Self-Assembly of Tris,(2-ureidobenzyl)amines: A New Type of Capped, Capsule-Like Dimeric Aggregates Derived from a Highly Flexible Skeleton

Article abstract of DOI:10.1002/chem.200305559

A set of tris(2-ureidobenzyl)-amines 3 was prepared and their dimerization processes thoroughly investigated. In spite of their inherent flexibility, tris(ureas) 3 form dimeric aggregates both in the solid state and in solution. Evidence for the existence

Full text of DOI:10.1002/chem.200305559

FULL PAPER
Self-Assembly of Tris(2-ureidobenzyl)amines: A New Type of Capped,
Capsule-Like DimericAggregates Derived from a Highly Flexible Skeleton
Mateo AlajarÌn,*[a] Aurelia Pastor,[a] RaÇl-çngel Orenes,[a] Jonathan W. Steed,[b] and
Ryuichi Arakawa[c]
Abstract: A set of tris(2-ureidobenzyl)-
amines 3 was prepared and their dime-
rization processes thoroughly investi-
gated. In spite of their inherent flexibil-
ity, tris(ureas) 3 form dimeric aggre-
gates both in the solid state and in sol-
ution. Evidence for the existence of
these dimeric species was provided by
a combination of techniques (X-ray
analysis, NMR and IR spectroscopy,
and ESI-MS). The association con-
stants and thermodynamic parameters
for the dimerization processes of se-
lected tris(ureas) were determined and
show that they are enthalpically driven.
Heterodimerization experiments in sol-
ution reveal a high degree of self-rec-
ognition or narcissistic self-sorting. On
the other hand, desymmetrized tris(ur-
eas) derived from 3 self-assemble with
modest regioselectivities depending on
the terminal substituent of every urea
functionality.
Keywords: dimerization ¥ hydrogen
bonds ¥ molecular recognition ¥ self-
assembly ¥ ureas
Introduction
is the reason why in most cases self-assembling subunits are
based on conformationally restricted systems.
Complementarity and preorganization are key concepts in
supramolecular chemistry.[1] Thus, for several units to self-as-
semble they have to possess binding sites with the correct
electronic character (polarity, hydrogen bond donor/accept-
or ability, hardness or softness, etc.) to complement each
other. Furthermore, if these units do not undergo a signifi-
cant conformational reorganization upon self-assembling
they are said to be preorganized. In this case, the entropic
penalty associated with the loss of degrees of freedom of the
individual subunits upon self-association is minimized. This
The tribenzylamine unit provides an excellent scaffold for
supramolecular chemistry in spite of its flexibility. Nine rota-
tions per subunit (i.e., around bonds a c in Figure 1) and in-
version of the pivotal nitrogen atom must be restricted in as-
semblies incorporating rigid tribenzylamine subunits.
[a] Prof. Dr. M. AlajarÌn, Dr. A. Pastor, R.-ç. Orenes
Departamento de QuÌmica Orgµnica, Facultad de QuÌmica
Universidad de Murcia
Figure 1. Tribenzylamine functionalized at the 2-position. Letters a, b,
and c represent the bond rotations which would be restricted in a tripod
tripod assembly.
Campus de Espinardo, Murcia-30.100 (Spain)
Fax : (+34)968-364149
E-mail: alajarin@um.es
[b] Dr. J. W. Steed
Department of Chemistry
King×s College London
Strand, London WC2R 2LS (UK)
Nevertheless, tribenzylamines properly functionalized at
every arm assemble with other tripodal subunits as recently
described in the literature.[2] Thus, chiral macrobicyclic tri-
phosphazides and triphosphazenes have been prepared by
tripod tripod coupling of tris(2- and 3-azidobenzyl)amines
with 1,1,1-[tris(diphenylphosphino)methyl]ethane. Based on
this success, our investigations have been aimed at the syn-
thesis of self-assembling capsules containing the tribenzyl-
amine moiety in which each arm of this tripodal molecule is
[c] Prof. Dr. R. Arakawa
Department of Applied Chemistry
Kansai University
Suita, 564 8680 Osaka (Japan)
Supporting information for this article is available on the WWW
under http://www.chemeurj.org or from the author, including 2D
ROESY spectra for tris(ureas) 3a, 3d, and 3g and H NMR spectra
1
in CDCl3 for tris(ureas) 6a c.
1383
Chem. Eur. J. 2004, 10, 1383 1397
DOI: 10.1002/chem.200305559
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

FULL PAPER
Table 1. Synthesis of tris(amines) 2 and tris(ureas) 3.
endowed with secondary urea groups, which are excellent
for hydrogen bonding interactions.[3]
Entry Compound R1
R2
Solvent T [8C] Yield [%]
To our delight, tris(2-ureidobenzyl)amines associate in
solution and in the solid state to give dimeric aggregates.[4]
These dimers are composed of two enantiomeric units asso-
ciated through their urea residues (Figure 2). The interacting
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
2a
2b
3a
3b
3c
3d
3e
3 f
3g
3h
3i
H
Me
H
Me
H
Me
H
H
75[a](90)[b]
73[a]
4-MeC6H4
4-MeC6H4
4-nBuC6H4
4-nBuC6H4
4-MeOC6H4
4-CF3C6H4
Bn
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3 reflux
CHCl3 reflux
CHCl3 reflux
CHCl3 reflux
20
20
20
20
20
20
87
87
77
77
86
89
81
91
58
80
62
64
77
H
Me
H
Bn
CH2=CHCH2
nPr
3j
3k
3l
Me
Me (S)-Ph(Me)CH CHCl3 reflux
Me
H
iPr
DMF
DMF
80
80
3m
2,6-Me2C6H3
[a] By method A. [b] By method B.
Figure 2. Schematic view of the self-assembly between two tris(2-ureido-
benzyl)amine subunits showing the belt of hydrogen-bonded ureas.
ureido functionality), the more drastic the reaction condi-
tions that were required regardless of the reactivity of the
corresponding isocyanate.
The synthesis of the tris(urea) 3n was conducted in a two-
step synthetic sequence[8] by starting from the tris(amine) 2a
(Scheme 2). Thus, treatment of 2a with 1,1,1,3,3,3-hexa-
urea functionalities form a belt of 12 hydrogen bonds, a
rather singular motif that has only been previously observed
by Rebek Jr. et al.,[5] Bˆhmer et al.,[6] and de Mendoza
et al.[7] for ureidocalix[4]- and -[6]arenes. Herein we present
a full study of these self-assembling systems which includes
complete characterization of the dimeric aggregates in the
solid state and solution, the determination of thermodynam-
ic parameters for the dimerization process, the formation of
heterodimeric species, and the study of the regioselectivity
in the self-assembly of tris(ureas) lacking C3v symmetry.
Results and Discussion
Scheme 2. Synthesis of the tris(urea) 3n. a) i) HMDS, nBuLi, DMDTC,
THF, ꢀ78!208C, 6 h; b) MeNH2, MeOH, reflux, 15 h.
Synthesis: The readily available tris(2-azidobenzyl)amines
1[2b] (Scheme 1) were converted into the tris(amines) 2 in
good yields by two alternative methods: A) reduction with
methyldisilazane (HMDS) and S,S-dimethyldithiocarbonate
(DMDTC) led to the tris(thiocarbamate) 4, which was then
allowed to react with MeNH2 to give the tris(urea) 3n with
three pendant N-methylureido groups.
Solid-state structure of 3d:[9] Diffraction-quality crystals of
the tris(urea) 3d were obtained by recrystallization from
CH2Cl2/Et2O. The single-crystal X-ray analysis revealed the
existence of two independent dimeric aggregates 3d¥3d in
the crystal lattice with slightly different shapes, one of which
is shown in Figure 3.
Scheme 1. Synthesis of tris(ureas) 3. a) Method A: LAH, Et2O, 20 8C, 4 h
or method B: i) PMe3, THF, 08C, 20 min; ii) THF/H2O, 20 8C, 18 h;
b) R2NCO, solvent, temperature (see Table 1).
As found in a previous example,[4] the dimers are formed
by two C3-symmetric enantiomeric tripods turned 608 with
respect to each other and encircled by a belt of six hydro-
gen-bonded ureas. This arrangement results in S6 symmetry
for the dimeric core. The conformationally restricted triben-
zylamine skeleton adopts a propeller-like conformation,
which can be visualized from the view along the C3 axis
(Figure 3a).
Notably, the formation of the aggregate is accompanied
by a chiral self-discrimination event, since one enantiomeric
tripod recognizes its mirror image. Very few examples of
such self-discrimination have been described thus far.[10]
LiAlH4 (LAH) or B) sequential treatment with PMe3 and
tetrahydrofuran (THF)/H2O (Table 1). Tris(2-ureidobenzyl)-
amines 3a m were obtained from 2 in 58 91% yield by
treatment with the corresponding isocyanate. The data in-
cluded in Table 1 highlight several factors: in particular, the
more sterically encumbered the terminal substituent at the
ureido functionality (e.g., aromatic 2,6-disubstitution or sec-
ondary carbons next to the terminal nitrogen atom of the
1384
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1383 1397

Tris(2-ureidobenzyl)amine Self-Assembly
1383 1397
Table 2. Crystallographic data for 3d¥3d.
Parameter
Value
empirical formula
formula weight
T [K]
C58H71Cl2N7O3
985.12
100(2)
wavelength [ä]
crystal system
space group
a [ä]
b [ä]
c [ä]
0.71073
trigonal
≈
R3
21.256(3)
21.256(3)
42.469(7)
90
a [8]
b [8]
90
g [8]
120
16617(4)
12
1.181
0.166
V [ä3]
Z
1 [gcmꢀ3
]
]
m [mmꢀ1
F(000)
6312
crystal size [mm3]
q range [8]
h
0.50î0.40î0.30
2.64 25.00
ꢀ25 to 22
ꢀ25 to 24
ꢀ50 to 44
25372
6496
0.0976
408
k
l
reflections collected
unique reflections
R(int)
no. of parameters
no. of restraints
R1 (I>2s(i))
wR2 (I>2s(i))
R1 (all data)
wR2 (all data)
0
0.0666
0.1542
0.1036
0.1700
0.269/ꢀ0.234
Figure 3. Top (a) and side view (b) of the dimeric structure 3d¥3d. The
belt of hydrogen-bonded urea moieties is indicated by dotted lines.
D1[eäꢀ3
]
The diaryl urea units of every arm are far from planarity
with approximate interplanar angles of 46.4 46.68/48.8 49.08
between the two aryl rings. The X-ray structure of 3d¥3d
(Table 2) also shows weak edge-to-face p-stacking interac-
tions between the aromatic rings of the tribenzylamine skel-
eton and the pendant aromatic rings from the other subunit.
Interestingly, the urea-type hydrogen bonds are very dif-
ferent with the distance N¥¥¥O=C (2.84 2.89 ä) for the urea
nitrogen atoms bearing the pendant 4-butylphenyl substitu-
ents being rather shorter than the distance N¥¥¥O=C (3.12
3.20 ä) for the urea nitrogen atoms attached to the triben-
zylamine skeleton. In contrast to the new dimer 3d¥3d, the
previously described X-ray structure of 3g¥3g (Figure 4a)
has a more symmetrical belt of hydrogen bonds with distan-
ces of 2.90 3.02 ä (Figure 4b).[4]
These differences in the arrangement of the hydrogen
bond network between 3d¥3d and 3g¥3g and the lack of p-
stacking interactions in 3g¥3g could explain important dif-
ferences in their respective behavior in solution (see below).
A detailed inspection of both crystal structures reveals
that the success of the dimerization process seems to be de-
termined by a subtle interplay of conformational features:
the propeller-like topology around the pivotal nitrogen
atoms of the tripodal moieties, the tilt of the 1,2-disubstitut-
ed arene rings in relation to the C3 axis passing through
those nitrogen atoms, and the dihedral angles between the
mean planes of the urea cores with respect to their adjacent
arene rings. The consonance of these structural fragments
provides the unique conformation shown in Figures 3 and
4a which allows the effective interdigitation of the urea
units. Any appreciable change in some of these fragments
would render the dimerization process less favorable by de-
stroying the optimal alignment of the 12 hydrogen bonds
within the urea belt. This factor may account for the high
degree of narcissistic self-sorting shown by these aggregates
in solution (see below).
Dimers 3d¥3d form capsule-like aggregates with an inter-
nal cavity. The distance between the two pivotal nitrogen
atoms in 3d¥3d (5.911/6.307 ä) relative to 3g¥3g (5.511 ä)
implies a slightly larger cavity in the former although no
guest was found inside.
Behavior in solution of tris(ureas) 3a j and 3n: These tris-
(ureas) self-assemble in solution in solvents that provide no
competitive hydrogen bonding (e.g., CDCl3, CD2Cl2, and
benzene) to give dimers linked by 12 hydrogen bonds of
similar geometry to those depicted in the X-ray structures.
Evidence for these self-assembling processes was provided
by a combination of different experiments (i.e., 1H and
13C NMR data recorded in different solvents, 2D ROESY
experiments, IR spectroscopy, and ESI-MS measurements).
Furthermore, encapsulation experiments and heterodimeri-
zation processes have been investigated.
1H and 13C NMR data: For all tris(ureas) the number and
1
pattern of the H NMR signals in polar competitive hydro-
1385
Chem. Eur. J. 2004, 10, 1383 1397
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. AlajarÌn et al.
FULL PAPER
gen-bonding solvents such as [D6]DMSO and [D4]methanol
corresponded to those expected for monomers of averaged
C3v symmetry (Figures 5a and 6a). The most representative
signal was that for the methylenic protons of the (ArCH2)3N
fragment: a singlet at d=3.43 3.64 ppm.
However, a completely different picture was observed in
noncompetitive solvents such as CDCl3. Thus, two sets of
signals emerged corresponding to two species of different
symmetry. The ratio in which both species were present in
CDCl3 depends on the substituent R2 to a great extent.
While for tris(ureas) 3a f and 3n only the signals attributed
to the less symmetric species were apparent (Figure 5b), the
spectra for the tris(N-alkyl)ureas 3g j were interpreted as
corresponding to equilibrium mixtures of both compounds
(Figure 6c). The more symmetric species, assigned to the
monomer when it was detected, featured the expected pat-
tern consistent with an averaged C3v symmetry. The chemi-
cal shifts for nearly all this set of signals (except for the NH
protons) were very similar to those measured in [D6]DMSO
(Figures 6a and c). On the other hand, the less symmetrical
species typically revealed the splitting of the singlet corre-
sponding to the methylenic protons of the (ArCH2)3N frag-
ment into two doublets (J=14.5 15.9 Hz) (Figures 5b and
6c).
The 1H NMR data for the less symmetrical species are
consistent with the hydrogen-bonded dimeric aggregates of
S6 symmetry revealed by the crystal structures of 3d¥3d and
3g¥3g (Scheme 3 and Figures 3 and 4a).
Notably, all these equilibria could be shifted toward the
monomer by: 1) decreasing the concentration of the tris(ur-
eas), 2) increasing the temperature (Figure 6b,c), and 3) by
addition of competitive hydrogen-bonding solvents such as
[D6]DMSO.
Figure 4. a) Top view of the dimeric structure 3g¥3g. The belt of hydro-
gen-bonded urea moieties is indicated by dotted lines. b) Comparison of
the pattern of the hydrogen bonding network for 3d¥3d and 3g¥3g based
on the crystallographic data.
The shift to lower field of the signals for the NH groups
supports the engagement of the
urea functionalities in an or-
dered, extensively hydrogen-
bonded system in solution when
compared to a reference urea
(Scheme 4). Notably, the chemi-
cal shifts of these protons re-
mained
concentration-inde-
pendent in the range 10.0
0.3 mm.
In
contrast,
the
1H NMR spectra of most ureas
(e.g., diphenyl urea) are highly
concentration-dependent.[11]
The upfield shifts observed
for the methylenic protons next
to the pivotal nitrogen atom
and for those located at the ter-
minal substituents of the urea
functionalities in the dimeric
tris(ureas) 3a f (schematically
represented by 3d¥3d in
Scheme 5) were even more in-
formative. These results reflect-
ed the mutual anisotropy expe-
rienced by the tribenzylamine
Figure 5. 1H NMR spectra (300 MHz) of 3a a) in [D6]DMSO and b) in CDCl3 at 296 K; asterisks label the sig-
nals for residual water.
1386
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1383 1397

Tris(2-ureidobenzyl)amine Self-Assembly
1383 1397
Figure 6. 1H NMR spectra (300 MHz) of 3g a) in [D6]DMSO at 296 K; in CDCl3 at b) 323 K, c) 296 K, and d) 213 K; asterisk labels the signal for residual
water.
Scheme 4. Chemical shifts (CDCl3) for the NH resonances in 3a¥3a and
3g¥3g compared to a reference urea.
Scheme 3. Self-association of tris(ureas) 3 in solution of noncompetitive
hydrogen-bonding solvents.
lent, did not display upfield shifts presumably as a result of
unit and the pendant aromatic substituents owing to the in-
tercalation of the six arms in the dimeric structure.
lacking this peculiar arrangement of intercalating aromatic
rings.
In contrast, the methylenic protons next to the pivotal ni-
trogen atom in dimeric tris(ureido)amines 3g j (schemati-
cally represented by 3g¥3g in Scheme 5), although inequiva-
The appearance of rather different d values (Dd=
1.6 ppm) for the resonances owing to the two methylenic
protons of the pendant alkyl groups (R2 =CH2R) was also
1387
Chem. Eur. J. 2004, 10, 1383 1397
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. AlajarÌn et al.
FULL PAPER
NOE contacts are illustrated in Scheme 5 and nicely support
the formation of a dimeric aggregate in CDCl3. The most re-
vealing cross peaks were those relating the tribenzylamine
core with the pendant urea protons. These nuclei are too far
apart in the monomeric structure to allow these cross peaks
to be assigned to intramolecular NOE contacts. Notably,
they were not present in the spectra measured in
[D6]DMSO.
All the protons involved in NOE contacts were examined
in the corresponding X-ray structures (3d¥3d and 3g¥3g)
and have interatomic distances below 3.5 ä. This fact pro-
vides an additional proof that the geometry of the dimers in
the solid state remains in solution.
Scheme 5. Chemical shift differences (ppm) between the dimer and the
corresponding monomer for selected protons in 3d¥3d and 3g¥3g
(CH2Npiv not unequivocally assigned). Arrows indicate important NOE
contacts from a 2D ROESY spectrum (600 MHz).
IR measurements: Another telltale sign of the engagement
of the NH groups in hydrogen bonding was provided by the
FTIR spectra of 3a (13.7 mm) and 3g (16.4 mm) in CHCl3
solution. The spectra showed exclusively the hydrogen-
bonded NH stretching band at 3317 3327 cmꢀ1 (non-hydro-
gen-bonded NH stretches usually appear as a weak and
sharp band above 3400 cmꢀ1).[12]
noticeable in the spectra of dimeric aggregates of tris(ureas)
3g j. The aromatic rings of the tribenzylamine skeleton pro-
vide the anisotropic environment that determines the shield-
ing of only one of these benzylic protons. This proton was
assigned as that appearing at lower d values and the assign-
ment was confirmed on the basis of the ROE contacts be-
tween the signal due to this proton and those corresponding
to the tribenzylamine aryl protons (see structure 3g¥3g in
Scheme 5). These cross peaks were not observed for the
other benzylic proton.
ESI-MS spectra: Although mass spectrometry only reflects
the properties of gas-phase species, the correlation between
gas phase and solution is often reliable for ESI-MS, and con-
sequently this method has recently been used to analyze sol-
ution-phase aggregation processes.[13]
The dimeric assemblies of tris(ureas) 3a, 3g, and 3h were
detected by ESI-MS experiments. The spectra measured in
CHCl3 had base peaks for the respective protonated mono-
mers and the corresponding molecular ions for the protonat-
ed dimers 3a¥3a (m/z 1463), 3g¥3g (m/z 1464), and 3h¥3h
(m/z 1547) albeit with very low intensities (Figure 7). These
low abundances may be explained by taking into account
that the use of solvents that do not compete for hydrogen
bonds in ESI-MS usually requires an ion-labeling step (e.g.,
Na+/crown ether complexes,[14] anions,[15] and metal[16] or
quaternary ammonium[17] cations), which is not the case
here; with our dimers, protons provide the charge needed
for ESI-MS detection.
On the other hand, the combination of two monomers
can produce three structurally different dimeric aggregates
(two homodimers and one heterodimer) with three different
masses. An equimolar solution of 3g and 3h afforded a
nearly statistical mixture (1:2:1) of the three species 3g¥3g,
3h¥3h, and 3g¥3h detected in the ESI-MS spectra by their
respective protonated molecular ions. These findings almost
exactly parallel those observed by NMR experiments (see
below).
The 13C NMR spectra of 3g j measured in CDCl3 also re-
vealed the involvement of the urea carbonyl groups as hy-
drogen bond acceptors in the dimeric aggregates. Their d
values (d=157.7 158.3 ppm) appeared downfield relative to
those in the corresponding monomers (d=154.9
155.2 ppm).
To provide semiquantitative data on the relative stability
of the dimers, CDCl3 solutions were titrated with
[D6]DMSO until the dimeric species signals were no longer
visible (Table 3). The dimeric assemblies of N-aryl-substitut-
ed tris(ureas) 3a, 3c, and 3d are therefore more stable than
those of the N-alkyl-substituted 3g, 3h, and 3j.
Table 3. Volume of [D6]DMSO required to totally shift the equilibrium
towards the monomeric species.
Entry
Urea
R1
R2
%[D6]DMSO[a,b]
1
2
3
4
5
6
3a
3c
3d
3g
3h
3j
H
H
Me
H
Me
Me
4-MeC6H4
4-nBuC6H4
4-nBuC6H4
Bn
Bn
nPr
50
50
51
30
27
31
All these results make it difficult to distinguish between
the formation of dimeric capsule-like aggregates or other
unspecific associations in the gas phase. Nevertheless, it
seems unlikely that the capsule-like structure, which accord-
ing to the NMR experiments is present in solution, is trans-
formed into a nonspecific aggregate during the electrospray
process; however, this possibility cannot be excluded.
[a] With respect to the volume of CDCl3. [b] [D6]DMSO was added to a
solution of CDCl3 until the monomer/dimer ratio was ꢁ95:5 (200 MHz
1
or 300 MHz) in the H NMR spectra.
2D ROESY experiments: Two-dimensional ROESY experi-
ments in CDCl3 and [D6]DMSO were employed to obtain
structural details of aggregates 3a¥3a, 3d¥3d, and 3g¥3g in
solution (see Supporting Information). The most significant
Encapsulation behavior: Usually, the addition of a suitable
guest, often a solvent molecule, of complementary size and
1388
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1383 1397

Tris(2-ureidobenzyl)amine Self-Assembly
1383 1397
for the respective monomers
and dimers were slow on the
NMR time scale, the popula-
tions of both species were de-
termined by integration of their
respective
peaks
in
the
1H NMR spectra. This provided
a convenient means of deter-
mining the association con-
stants at different tempera-
tures.[20] The values of DG8,
DH8, and DS8 were obtained
for the dimerization equilibria
of tris(ureas) 3a, 3g, and 3h
(Table 4) from the correspond-
ing van’t Hoff plots (Figure 8).
These values indicate the
large and compensating effects
operating in the dimerization
processes, since they are en-
thalpically favorable and en-
Figure 7. ESI mass spectrum of a CHCl3 solution of 3a.
tropically very unfavorable. The
shape favors the formation of discrete aggregates by acting
as a template.[18]
negative enthalpic component may be the result of the stabi-
lizing interactions between the six urea functionalities by hy-
drogen bonding. Likewise, the high negative DS8 values
In our case, encapsulation studies of small organic mole-
cules such as MeI and CH2Cl2, which are good guests for
tris(3-ureidobenzyl)amines,[19] were performed for 3a¥3a.
After dissolving the sample in CDCl3, an excess of the guest
Table 4. Association constants and thermodynamic parameters for the
dimerization of tris(ureas) 3a, 3g, and 3h in CDCl3.
1
was added and the H NMR spectrum was recorded at 20
[a]
Entry
Dimer
Kass
DG8
DH8
DS8
[mꢀ1
]
[kJmolꢀ1
]
[kJmolꢀ1
]
[Jmolꢀ1 Kꢀ1]
and ꢀ608C. Unfortunately, the spectra did not show any
change relative to those measured without the guest. Fur-
thermore, no signal for an encapsulated molecule was found
confirming that no species occupied the interior of the
cavity. These findings agree with the results revealed by the
X-ray structures (see above) and may be explained as result-
ing from the small dimensions of the cavity.
1
2
3
3a¥3a
3g¥3g
3h¥3h
91200
4000
1000
ꢀ28.3
ꢀ20.6
ꢀ17.1
ꢀ49.3
ꢀ74.9
ꢀ64.0
ꢀ70.6
ꢀ182.2
ꢀ157.6
[a] At 298 K.
Behavior in solution of tris(ureas) 3k m: As mentioned
above, the nature of the pendant substituent at the urea
functionality decisively influences the ratio of monomer/
dimer present in CDCl3 solutions. Thus, for tris(N-arylurei-
dobenzyl)amines 3a f and tris(N-methylureidobenzyl)amine
3n the monomer was present in tiny concentrations. In con-
trast, for tris(N-alkylureidobenzyl)amines 3g j the mono-
mer/dimer ratio was higher. Consistent with the same trend,
tris(ureas) 3k m (Table 1) do not form dimeric aggregates
1
in solution at all. Their H NMR spectra only have signals
for a species of averaged C3v symmetry at chemical shifts
rather similar to those measured in competitive solvents
such as [D6]DMSO which were assigned to the correspond-
ing monomers. This fact confirms that sterically encumbered
R2 residues make the dimerization process unfavorable.
For the particular case of the enantiomerically enriched
tris(urea) (S)-3k, the formation of both the homochiral spe-
cies (S)-3k¥(S)-3k and the heterochiral species (S)-3k¥(R)-
3k was tested with negative results.
Figure 8. Van’t Hoff plots (r2 >0.996) for the association processes of tris-
(ureas) 3a (^), 3g (&), and 3h (~) in CDCl3 over the temperature
range 295 337 K.
measured must account for the reduction of conformational
freedom during dimerization.
Notably, this loss of freedom is rather acute for 3g¥3g
(DS8=ꢀ182.2) compared to 3a¥3a (DS8=ꢀ70.6) which may
be related to two facts: 1) a more ordered hydrogen bond
network of 3g¥3g compared to 3a¥3a[21] (Figure 4b) revealed
by the X-ray structures, and 2) a less significant loss of con-
Determination of the thermodynamicparameters of the di-
merization process: Since the association dissociation rates
1389
Chem. Eur. J. 2004, 10, 1383 1397
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. AlajarÌn et al.
FULL PAPER
formational freedom on going from monomer 3a to dimer
3a¥3a than in the case of formation of 3g¥3g, since 3a is
more preorganized owing to conjugation between the urea
and the pendant aryl groups.
The association constants for the formation of three heter-
odimeric assemblies (Table 6) were calculated by using
equations described by Cram.[20]
Additionally, the more symmetrical belt of 3g¥3g compris-
es twelve strong hydrogen bonds compared to six strong and
six weak hydrogen bonds for 3a¥3a. This fact is consequent-
ly reflected by a more negative value of DH8 (ꢀ74.9 versus
ꢀ49.3) for the former. Notably, the weak p-stacking interac-
tions present in 3a¥3a and the higher acidity of their urea
hydrogen atoms do not compensate this effect (the same ar-
guments may be applied to 3h¥3h).
Table 6. Association constants for the formation of homodimeric and
heterodimeric assemblies of tris(ureas) 3a, 3g, and 3h.
[a,b]
Entry
Assemblies
Kass
1
2
3
4
5
6
3a¥3a
3g¥3g
3h¥3h
3a¥3g
3a¥3h
3g¥3h
91200
4000
1000
2200
2100
7900
[a] mꢀ1. [b] Calculated at 298 K.
Heterodimerization processes: The combination of two
monomers can produce three structurally different dimeric
aggregates (two homodimers and one heterodimer). These
processes have frequently been used to verify dimerization
of tetraureido[4]calixarenes in solution[6a,c] and the gas
phase.[17c]
Isaacs and co-workers[22] have investigated theoretically
the variables that affect the fidelity of self-sorting processes:
one is how large the difference between the equilibrium
constants for homomeric versus heteromeric aggregation is
sufficient to drive narcissistic self-sorting. They found that a
10-fold difference in favor of the homomeric aggregate is
more than enough, although these studies were conducted
by fixing the values for the equilibrium constants of both
homodimeric assemblies to be 106 mꢀ1.
The formation of the corresponding heteromeric assem-
blies between tris(ureas) 3a, 3d, 3 f, 3g, and 3h was investi-
1
gated by H NMR spectroscopy. Since these tris(ureas) are
self-complementary, it would be reasonable to expect that
they would also complement each other. The formation of
hybrid aggregates was induced by dissolving equimolar
quantities of two different tris(ureas) in CDCl3.
As depicted in Table 5, the nature of the terminal sub-
stituent at the urea functionality determines the degree of
heterodimerization, in parallel to what we have previously
Thus, for the system comprising monomers 3a and 3g, ho-
modimers 3a¥3a (Kass =91200) and 3g¥3g (Kass =4000) and
the heterodimer 3a¥3g (Kass =2200), we found the following
distribution of molar fractions: c3a3a =0.94 (c3a =0.02 and
c3a3g =0.04) and c3g3g =0.87 (c3g =0.09 and c3a3g =0.04).
These values reveal that the respective homodimeric assem-
blies are the major species and confirm the findings descri-
bed by Isaacs for species which present narcissistic self-sort-
ing behavior (slight differences may be due to the fact that
both homodimeric association constants are not equal).
Table 5. Percentage[%] of heterodimerization between tris(ureas) 3a,
3d, 3 f, 3g, and 3h in CDCl3.[a]
3a
3d
3 f[b]
3g
3h
3a
3d
3 f
3g
3h
27
61
80
5
5
12
9
7
31
51
Analogous results were found for 3a¥3h (c3a3a =0.90, c3a
0.02, c3h3h =0.71, c3h =0.21, and c3a3h =0.08).
=
[a] Calculated according to the equation: [AB]î100/([AB]+[AA]+
[BB]). [b] Measured in C2D2Cl4.
As an exception, heterodimers formed with tris(urea) 3 f
(the experiments were conducted in C2D2Cl4 as a result of
insolubility in CDCl3) displayed high levels of heterodimeri-
zation; in other words, these heterodimeric assemblies
showed higher stabilities compared to the rest of the hetero-
dimers investigated in Table 5. These findings may be ration-
alized in terms of the increased acidity of the 4-trifluoro-
phenyl-substituted urea NH protons which complements the
relative basicity of the tris(ureas) 3a, 3d, 3g, and 3h. As has
been previously established,[23] the strong dependence of hy-
drogen bonding on electron distribution provides a facile
means of controlling the strength of this interaction through
substituent effects.
Finally, we investigated if tris(2- and 3-ureidobenzyl)a-
mines were complementary, since the 3-isomers also form
dimeric species of analogous structure in CDCl3 solution.[19]
Thus, we tried the heterodimerization of 3a or 3g with the
tris(3-ureidobenzyl)amine 5. However, the respective hybrid
species were detected in 18% and 0%, respectively, thus
showing again the high tendency of tris(2-ureidobenzyl)-
amines to narcissistic self-aggregation.
observed in the corresponding homodimerization processes.
The hybrid species was formed in a statistical ratio only
when these pendant substituents were identical (3g¥3h).
Surprisingly, the change of a 4-tolyl (3a) by a 4-butyl-
phenyl (3d) terminal substituent led to a two-fold decrease
in the percentage of heterodimerization with respect to the
statistical ratio (27% versus 50%). Finally, mixtures of aryl/
benzyl-substituted tris(ureas) (3a¥3g, 3d¥3g, 3a¥3h, or
3d¥3h) showed less than 9% of heterodimerization. The
degree of heterodimerization was independent of the sol-
vent (similar percentages of heterodimerization were found
in [D8]toluene and C2D2Cl4).
On the basis of all these results, tris(2-ureidobenzyl)-
amines can be considered to behave with a high degree of
self-recognition or narcissistic self-sorting. This is not a very
common phenomenon and is defined as the high-fidelity rec-
ognition of self from nonself.[22]
1390
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1383 1397

Tris(2-ureidobenzyl)amine Self-Assembly
1383 1397
Self-assembly of desymmetrized tris(2-ureidobenzyl)amines
6: As mentioned above, monomeric tris(2-ureidobenzyl)-
amines adopt C3v symmetry in solution, which is reduced to
C3 when they are integrated into the dimeric assembly. In-
terdigitation of the six arms of the two tripods converts the
C3 axis of each monomer to an overall S6 axis for the dimer.
Although dimeric assemblies of tris(ureas) 3 are achiral,
their geometry offers the possibility to achieve chirality in
the assemblies, for instance by the dimerization of tris(ur-
eas) with different substituents in each arm. In the particular
case of two identical arms and a different one (Cs symmetry
for the monomer), three different assemblies may be
formed: two enantiomeric dimers of C1 symmetry (A and B
in Figure 9) and another dimeric assembly of Ci symmetry
Scheme 6. Reagents and reaction conditions for the synthesis of tris-
(ureas) 6. a) NaI, acetone, 208C, 20 h; b) 2-azidobenzylamine, Na2CO3,
CH3CN, reflux, 24 h; c) i) PMe3, THF, 08C, 30 min; ii) H2O/THF, 208C,
20 h; d) R1NCO, CH2Cl2, 208C, 24 h; e) H2, PtO2, THF, 208C, 18 22 h;
f) R2NCO, CH2Cl2, 208C, 16 18 h.
with an isocyanate the tribenzylamines 9a and 9b were iso-
lated in 98% yield. Compounds 6a d were obtained from
9a,b by sequential catalytic hydrogenation (10a: 74%; 10b:
84%) and treatment with the corresponding isocyanate
(Table 7).
The self-assembly of 6a c in CDCl3 solutions was investi-
gated (6d was highly insoluble in CDCl3 or C2D2Cl4). Re-
gioisomers A/B and C interconvert by dissociation and re-
combination of the two subunits. Since this dissociation re-
combination process is slow on the NMR time scale, the
ratio of both regioisomeric species A/B and C present in the
equilibrium could be determined by integration of selected
signals (resonances of terminal NHs). As depicted in
Table 7, the ratio of both regioisomers was only slightly in-
fluenced by the electronic nature of the terminal residue at-
tached to the urea functionality.
Figure 9. Schematic representation of the symmetry properties of tris(ur-
eas) 6 consisting of two similar and one different terminal substituent of
the urea functionality (the directionality of the belt of hydrogen bonds is
symbolized by arrows).
(C), which is regioisomeric with the other two. The chirality
featured by dimers A/B is supramolecular, since it is due
only to the mutual arrangement of the two tris(ureas) in the
dimer.[24]
Taking into account these preliminary considerations, de-
symmetrized tris(ureas) 6 were prepared as depicted in
Scheme 6. Based on previous results found for tris(ureas)
with C3v symmetry, we anticipated that the regioselection
should be more pronounced for different terminal residues
than for different substituents at the tribenzylamine core.
The preparation started with the treatment of 2-nitrobenzyl-
chloride with NaI to give the corresponding iodide (96%
yield), which was then treated with 2-azidobenzylamine in
the presence of Na2CO3 to yield the tertiary amine 7 (91%).
The formation of the corresponding iminophosphorane by
reaction of 7 with trimethylphosphane followed by hydroly-
sis in THF/H2O led to the amine 8 (67 90%). After reaction
Since a 66:33 ratio of regioisomers corresponds to a statis-
tical distribution of A, B, and C (33:33:33), some degree of
Table 7. Yields[%] and regioselectivities in the association process of
tris(ureas) 6.
Entry
Urea
R1
R2
Yield[%]
A/B:C[a]
1
2
3
4
6a
6b
6c
6d
4-nBuC6H4
4-nBuC6H4
4-CH3OC6H4
4-CH3OC6H4
4-CF3C6H4
4-FC6H4
4-CF3C6H4
4-FC6H4
43
90
44
91
57:43
66:34
60:40
[b]
[a] Determined by integration of selected signals in their 1H NMR spec-
tra (400 MHz); error ꢂ5% of the stated value. [b] Value could not be
determined as a result of the insolubility of 6d in CDCl3 and C2D2Cl4.
1391
Chem. Eur. J. 2004, 10, 1383 1397
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. AlajarÌn et al.
FULL PAPER
Impact 400 infrared spectrophotometer, and melting points were taken
on a Reichert apparatus and are uncorrected.
regioselection was only found for 6a and 6c in favor of the
Ci regioisomer (C) (entries 1 and 3; Table 7). In contrast to
the desymmetrized tetraurea calix[4]arenes described by
Bˆhmer and co-workers, no influence in the regioisomeric
distribution was observed by changing the solvent from
CDCl3 to C2D2Cl4 or [D8]toluene.[24]
S,S-Dimethyl dithiocarbonate (DMDTC) was prepared according to a re-
ported procedure.[28]
CAUTION: Azido compounds may represent an explosion hazard when
concentrated under vacuum or stored neat. A safety shield and appropri-
ate handling procedures are recommended.
Interestingly, when a sample of 6a obtained by slow evap-
oration of a CDCl3 solution was redissolved in the same sol-
vent and its 1H NMR spectrum immediately recorded, it
showed a 36:64 ratio of C1:Ci regioisomers (see Supporting
Information)! After one day, the mixture of regioisomers
equilibrated and reached a similar ratio to that shown in
Table 7 (the results in Table 7 were achieved by recording
the spectra under equilibrium conditions, that is, 15 min
after being dissolved in CDCl3). This interesting result
seems to be an indication of a clear predominance of the Ci
regioisomer of 6a in the solid state. Unfortunately we did
not succeed in growing single crystals of tris(urea) 6a suita-
ble for X-ray determination. Efforts are currently underway
in our laboratories to investigate this phenomenon in more
depth.
General procedure for the synthesis of tris(2-aminobenzyl)amines 2:
Method A: The corresponding tris(azide) 1[2b] (2.03 mmol) was dissolved
in freshly distilled Et2O (10 mL) and slowly added to a suspension of
LiAlH4 (0.23 g, 6.09 mmol) in the same solvent (30 mL) at 08C under N2.
The mixture was stirred at this temperature for 0.5 h, warmed to 208C,
and stirred for 4 h more. The reaction mixture was then cooled to 08C
and treated with 10% aqueous NaOH (5 mL). After filtration over a pad
of Celite, the ethereal phase was separated and the aqueous phase was
extracted with CH2Cl2 (3î10 mL). The combined extracts were dried
over MgSO4, the solvent was evaporated (308C/75 Torr), and the residue
was purified by silica gel chromatography.
Method B: PMe3 in THF (1.0m, 7.24 mL, 7.24 mmol) was slowly added at
08C to a solution of the corresponding tris(azide) 1 (2.14 mmol) in fresh-
ly distilled THF (30 mL) under N2. The reaction mixture was then stirred
at this temperature until the band corresponding to the azide functionali-
ty (around 2100 cmꢀ1) disappeared from its IR spectrum (20 min approxi-
mately). At this time a white precipitate corresponding to the phospha-
zene was apparent in the mixture. THF (80 mL) and H2O (15 mL) were
then added and the reaction mixture was stirred at 208C for 18 h. After
removal of the organic solvent (308C/75 Torr), H2O (50 mL) was added
and the aqueous phase was extracted with CH2Cl2 (3î30 mL). The com-
bined extracts were dried over MgSO4, the solvent was evaporated
(308C/75 Torr), and the residue was purified by silica gel chromatogra-
phy.
Conclusion
Tris(2-ureidobenzyl)amines 3 proved to be avid self-assem-
blers in spite of their inherent flexibility, since they form di-
meric aggregates both in the solid state and solution in a va-
riety of noncompetitive solvents. Evidence for these dimeric
species, which are capped, capsule-like aggregates in which
the six hydrogen-bonded urea functionalities form a belt
around the equator of the molecule, was provided by a com-
bination of several techniques (X-ray analysis, NMR and IR
spectroscopy, and ESI-MS). Association constants and ther-
modynamic parameters for the dimerization processes of se-
lected tris(ureas) reveal that they are enthalpically driven al-
though the size of the terminal substituent is decisive in the
stability of the dimeric species. Tris(2-ureidobenzyl)amines 3
also present a high degree of narcissistic self-sorting as
shown by the investigation of heterodimerization processes.
Finally, the assembly of desymmetrized tris(ureas) 6 afford-
ed modest regioselectivities which depend on the electronic
nature of the terminal substituent at the ureido functionali-
ty.
Tris(2-aminobenzyl)amine (2a): The title compound was prepared ac-
cording to methods A and B in 75% and 90% yield, respectively. Purifi-
cation by silica gel chromatography, eluted first with 5:1 Et2O/hexanes
and subsequently with Et2O (Rf =0.46 in 5:1 Et2O/hexanes) afforded 2a
as colorless prisms (an analytical sample was obtained by recrystallization
from 1:4 CH2Cl2/Et2O). M.p. 195 2068C; 1H NMR (200 MHz, CDCl3,
258C, TMS): d=3.46 (s, 6H), 3.85 (s, 6H), 6.56 (dd, 3J(H,H)=8.4 Hz,
4J(H,H)=1.1 Hz, 3H), 6.67 (td, 3J(H,H)=7.3 Hz, 4J(H,H)=0.8 Hz, 3H),
7.03 7.11 ppm (m, 6H); 13C NMR (50 MHz, CDCl3, 258C): d=57.1 (t),
115.5 (d), 117.8 (d), 121.8 (s), 128.9 (d), 132.0 (d), 145.6 ppm (s); IR
(Nujol): n˜ =3463 (NH), 3428 (NH), 3350 cmꢀ1 (NH); MS (70 eV, EI): m/z
(%): 332 (4) [M+], 106 (100); elemental analysis calcd (%) for C21H24N4
(332.5): C 75.87, H 7.28, N 16.85; found: C 75.42, H 7.39; N 16.94.
Tris(2-amino-5-methylbenzyl)amine (2b): The title compound was pre-
pared in 73% yield according to method A. Purification by silica gel
chromatography, eluted first with 5:1 Et2O/hexanes and subsequently
with Et2O (Rf =0.41 in 5:1 Et2O/hexanes), afforded 2b as colorless
prisms (an analytical sample was obtained by recrystallization from 2:1
CH2Cl2/Et2O). M.p. 230 2368C; 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=2.20 (s, 9H), 3.41 (s, 6H), 3.80 (s, 6H), 6.46 (d, 3J(H,H)=
8.5 Hz, 3H), 6.84 6.87 ppm (m, 6H); 13C NMR (50 MHz, CDCl3, 258C):
d=20.4 (q), 57.1 (t), 115.7 (d), 122.1 (s), 126.8 (s), 129.4 (d), 132.6 (d),
143.1 ppm (s); IR (Nujol): n˜ =3461 (NH), 3367 cmꢀ1 (NH); MS (70 eV,
EI): m/z (%): 374 (20) [M+], 120 (100); elemental analysis calcd (%) for
C24H30N4 (374.5): C 76.97, H 8.07, N 14.96; found: C 76.75, H 8.35, N
15.13.
Experimental Section
General procedure for the synthesis of tris(ureas) 3a f: The correspond-
ing tris(amine) 2 (0.30 mmol) was dissolved in dry CH2Cl2 (5 mL) and
the isocyanate (0.90 mmol) was added under N2. After stirring at 208C
for 18 h the solvent was removed (308C/75 Torr) and Et2O (5 mL) was
added. The white solid was filtered and dried under vacuum. Further pu-
rification was conducted by recrystallization from the appropriate mix-
ture of solvents.
Single-crystal X-ray analysis of 3d: Crystallographic measurements were
carried out at 100 K. The structure was solved by using SHELXS-97[25]
and developed via alternating least-squares cycles and difference Fourier
synthesis (SHELXL-97[25]) with the aid of the program XSeed.[26] Inspec-
tion of the difference Fourier map revealed the presence of a highly dis-
ordered molecule of CH2Cl2 occupying a total of 2315 ä3 per unit cell.
This was treated by using the SQUEEZE procedure.[27]
General: 1H and 13C NMR spectra were measured on a Bruker AC 200
(1H: 200 MHz, 13C: 50 MHz), Varian Unity-300 (1H: 300 MHz, 13C:
75 MHz), or Bruker Advance 400 (1H: 401 MHz, 13C: 101 MHz) spectro-
photometer with TMS (d=0.00 ppm) or the solvent residual peak as in-
ternal standards. IR spectra were recorded on an FTIR Nicolet
Tris{2-[N’-(4-methylphenyl)ureido]benzyl}amine (3a): The title com-
pound was prepared in 87% yield according to the general procedure to
afford 3a as colorless prisms (an analytical sample was obtained by re-
crystallization from 1:1 CHCl3/Et2O). M.p. 234 2368C; 1H NMR
(300 MHz, [D6]DMSO, 258C, TMS, only monomer was observed): d=
2.23 (s, 9H), 3.64 (s, 6H), 7.01 7.06 (m, 9H), 7.16 (td, 3J(H,H)=7.5 Hz,
1392
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1383 1397

Tris(2-ureidobenzyl)amine Self-Assembly
1383 1397
3
4J(H,H)=0.9 Hz, 3H), 7.31 (d, J(H,H)=8.1 Hz, 6H), 7.56 7.59 (m, 6H),
3J(H,H)=7.5 Hz, 6H), 2.10 (s, 9H), 2.49 (t, 3J(H,H)=7.4 Hz, 6H), 3.59
(s, 6H), 6.90 (d, 3J(H,H)=8.1 Hz, 3H), 7.02 (d, 3J(H,H)=8.7 Hz, 6H),
7.11 (s, 3H), 7.28 7.33 (m, 9H), 7.87 (s, 3H), 8.59 ppm (s, 3H); 1H NMR
(300 MHz, CDCl3, 258C, TMS, only dimer was observed): d=0.90 0.95
(m, 18H), 1.23 1.24 (m, 24H), 2.15 (m, 12H), 2.44 (s, 18H), 3.04 (d,
2J(H,H)=14.9 Hz, 6H), 3.16 (d, 2J(H,H)=14.9 Hz, 6H), 6.24 (d,
3J(H,H)=8.4 Hz, 12H), 6.42 (d, 3J(H,H)=8.4 Hz, 12H), 7.00 (s, 12H),
7.29 (s, 6H), 7.43 (s, 6H), 8.03 ppm (s, 6H); 13C NMR (50 MHz,
[D6]DMSO, 258C): d=13.8 (q), 20.5 (q), 21.7 (t), 33.3 (t), 34.2 (t), 55.3
(t), 118.5 (2îd), 124.1(d), 127.9 (d), 128.4 (2îd), 130.1 (s), 130.4 (d),
132.6 (s), 134.7 (s), 135.6 (s), 137.5 (s), 153.5 ppm (s); 13C NMR (50 MHz,
CDCl3, 258C): d=14.0 (q), 21.6 (q), 22.4 (t), 33.4 (t), 34.5 (t), 53.1 (t),
117.7 (2îd), 127.3 (d), 127.9 (2îd), 128.5 (d), 128.6 (d), 132.1 (s), 135.5
(s), 135.7 (s), 136.1 (s), 136.4 (s), 156.0 ppm (s); IR (Nujol): n˜ =3352
(NH), 3291 (NH), 1661 cmꢀ1 (C=O); MS (FAB+): m/z (%): 900 (19) [M+
+1], 295 (100), 219 (30); elemental analysis calcd (%) for C57H69N7O3
(900.2): C 76.05, H 7.73, N 10.89; found: C 75.76, H 7.93, N 11.04.
7.90 (s, 3H), 8.66 ppm (s, 3H); 1H NMR (300 MHz, CDCl3, 258C, TMS,
only dimer was observed): d=1.87 (s, 18H), 3.09 (d, 2J(H,H)=14.7 Hz,
6H), 3.22 (d, 2J(H,H)=14.7 Hz, 6H), 6.17 (d, 3J(H,H)=8.4 Hz, 12H),
6.40 (d, 3J(H,H)=8.4 Hz, 12H), 7.07 (d, 3J(H,H)=7.8 Hz, 6H), 7.19 (t,
3J(H,H)=7.4 Hz, 6H), 7.28 (t, 3J(H,H)=7.4 Hz, 6H), 7.41 (s, 6H), 7.63
(d, 3J(H,H)=7.5 Hz, 6H), 7.94 ppm (s, 6H); 13C NMR (50 MHz,
[D6]DMSO, 258C): d=20.3 (q), 54.4 (t), 118.3 (2îd), 123.7 (d), 123.8 (d),
127.1 (d), 128.6 (d), 129.1 (2îd), 130.0 (s), 130.6 (s), 137.0 (s), 137.1 (s),
153.1 ppm (s); 13C NMR (75 MHz, CDCl3, 258C): d=20.3 (q), 53.4 (t),
117.9 (2îd), 126.2 (d), 126.5 (d), 128.3 (d), 128.6 (d), 128.9 (2îd), 131.3
(s), 134.7 (s), 135.4 (s), 136.5 (s), 155.9 ppm (s); IR (Nujol): n˜ =3322
(NH), 1655 cmꢀ1 (C=O); IR (CHCl3, 13.7 mm): n˜ =3317 (NH), 1658 cmꢀ1
(C=O); MS (FAB+): m/z (%): 754 (45) [M++Na], 732 (42) [M++1], 239
(95), 132 (61); elemental analysis calcd (%) for C45H45N7O3 (731.9): C
73.85, H 6.20, N 13.40; found: C 73.83, H 6.37, N 13.53.
Tris{5-methyl-2-[N’-(4-methylphenyl)ureido]benzyl}amine (3b): The title
compound was prepared in 87% yield according to the general proce-
dure to afford 3b as colorless prisms. M.p. 270 2728C; 1H NMR
(300 MHz, [D6]DMSO, 258C, TMS, only monomer was observed): d=
2.10 (s, 9H), 2.21 (s, 9H), 3.58 (s, 6H), 6.90 (dd, 3J(H,H)=8.1 Hz,
4J(H,H)=1.8 Hz, 3H), 7.02 (d, 3J(H,H)=8.3 Hz, 6H), 7.12 (s, 3H), 7.28
(d, 3J(H,H)=8.3 Hz, 6H), 7.33 (d, 3J(H,H)=8.1 Hz, 3H), 7.87 (s, 3H),
8.59 ppm (s, 3H); 1H NMR (300 MHz, CDCl3, 258C, TMS, a 82:18 mix-
ture of dimer and monomer was observed): d(dimer)=1.89 (s, 18H), 2.47
(s, 18H), 3.00 (d, 2J(H,H)=14.5 Hz, 6H), 3.16 (d, 2J(H,H)=14.5 Hz,
6H), 6.20 (d, 3J(H,H)=8.3 Hz, 12H), 6.38 (d, 3J(H,H)=8.3 Hz, 12H),
6.93 (d, 3J(H,H)=7.7 Hz, 6H), 7.00 (d, 3J(H,H)=7.7 Hz, 6H), 7.36 (s,
6H), 7.42 (s, 6H), 7.86 ppm (s, 6H); d(monomer)=2.27 (s, 18H), 3.49 (s,
Tris{2-[N’-(4-methoxyphenyl)ureido]benzyl}amine (3e): The title com-
pound was prepared in 86% yield according to the general procedure to
afford 3e as colorless prisms. M.p. 221 2228C; 1H NMR (200 MHz,
[D6]DMSO, 258C, TMS, only monomer was observed): d=3.63 (s, 6H),
3.70 (s, 9H), 6.84 (d, 3J(H,H)=8.8 Hz, 6H), 7.02 (t, 3J(H,H)=7.3 Hz,
3
3H), 7.16 (t, J(H,H)=7.3 Hz, 3H), 7.32 (d, 3J(H,H)=8.8 Hz, 6H), 7.53
1
7.59 (m, 6H), 7.89 (s, 3H), 8.61 ppm (s, 3H); H NMR (300 MHz, CDCl3,
258C, TMS, an 83:17 mixture of dimer and monomer was observed):
d(dimer)=3.12 (d, 2J(H,H)=14.7 Hz, 6H), 3.25 (d, 2J(H,H)=14.7 Hz,
6H), 3.47 (s, 18H), 6.15 6.24 (m, 24H), 7.10 (d, 3J(H,H)=7.8 Hz, 6H),
3
4
7.20 (td, J(H,H)=7.8 Hz, J(H,H)=1.2 Hz, 6H), 7.26 7.33 (m, 6H), 7.39
(s, 6H), 7.66 (d, 3J(H,H)=7.2 Hz, 6H), 7.90 ppm (s, 6H); d(monomer)=
3.58 (s, 6H), 3.76 (s, 9H), 6.77 ppm (d, J(H,H)=9.0 Hz, 6H), the rest of
3
3
6H), 6.77 (s, 3H), 7.13 ppm (d, J(H,H)=8.1 Hz, 6H), the rest of the sig-
nals are overlapped with those corresponding to the dimer; 13C NMR
(50 MHz, [D6]DMSO, 258C): d=20.3 (2îq), 55.0 (t), 118.4 (2îd), 123.9
(d), 127.8 (d), 129.0 (2îd), 129.9 (s), 130.2 (d), 130.4 (s), 132.5 (s), 134.7
(s), 137.2 (s), 153.4 ppm (s); 13C NMR (75 MHz, CDCl3, 258C, only dimer
was observed since the signals for the monomer were too weak): d=20.2
(q), 21.5 (q), 53.2 (t), 118.0 (2îd), 127.1 (d), 128.4 (d), 128.6 (2îd), 129.0
(d), 131.1 (s), 132.1 (s), 135.3 (s), 135.5 (s), 136.3 (s), 156.0 ppm (s); IR
(Nujol): n˜ =3318 (NH), 1660 cmꢀ1 (C=O); elemental analysis calcd (%)
for C48H51N7O3 (774.0): C 74.49, H 6.64, N 12.67; found: C 74.41, H 6.75,
N 12.74.
the signals are overlapped with those corresponding to the dimer;
13C NMR (50 MHz, [D6]DMSO, 258C): d=54.3 (t), 55.1 (q), 113.9 (2îd),
120.0 (2îd), 123.5 (d), 123.7 (d), 127.1 (d), 128.7 (d), 129.8 (s), 132.7 (s),
137.7 (s), 153.2 (s), 154.4 ppm (s); 13C NMR (75 MHz, CDCl3, 258C, only
dimer was observed since the signals for the monomer were too weak):
d=53.4 (t), 55.2 (q), 113.6 (2îd), 119.2 (2îd), 126.6 (d), 126.7 (d), 128.2
(d), 128.5 (d), 131.2 (s), 134.8 (s), 136.4 (s), 155.8 (s), 155.9 ppm (s); IR
(Nujol): n˜ =3320 (NH), 1657 cmꢀ1 (C=O); elemental analysis calcd (%)
for C45H45N7O6 (779.9): C 69.30, H 5.82, N 12.57; found: C 68.91, H 5.88,
N 12.56.
Tris(2-{N’-[4-(trifluoromethyl)phenyl]ureido}benzyl)amine (3 f): The title
compound was prepared in 89% yield according to the general proce-
dure to afford 3 f as colorless prisms. M.p. 258 2608C; 1H NMR
(300 MHz, [D6]DMSO, 258C, TMS, only monomer was observed): d=
3.63 (s, 6H), 7.05 (t, 3J(H,H)=7.5 Hz, 3H), 7.15 (t, 3J(H,H)=7.7 Hz,
3H), 7.52 (d, 3J(H,H)=7.5 Hz, 3H), 7.56 7.62 (m, 15H), 8.09 (s, 3H),
9.18 ppm (s, 3H); 1H NMR (300 MHz, C2D2Cl4, 258C, TMS, only dimer
was observed): d=2.93 (d, 2J(H,H)=14.7 Hz, 6H), 3.15 (d, 2J(H,H)=
14.7 Hz, 6H), 6.28 (d, 3J(H,H)=8.4 Hz, 12H), 6.83 (d, 3J(H,H)=8.4 Hz,
12H), 7.16 (d, J(H,H)=7.2 Hz, 6H), 7.30 (t, J(H,H)=7.5 Hz, 6H), 7.38
(t, 3J(H,H)=7.2 Hz, 6H), 7.57 7.60 (m, 12H), 8.11 ppm (s, 6H);
13C NMR (75 MHz, [D6]DMSO, 258C): d=54.3 (t), 117.8 (2îd), 121.7 (q,
2J(C,F)=31.8 Hz), 124.3 (d), 124.4 (d), 124.5 (q, 1J(C,F)=269.5 Hz),
126.0 (2îd), 127.2 (d), 128.8 (d), 130.8 (s), 136.5 (s), 143.5 (s), 152.9 ppm
(s); 13C NMR (75 MHz, C2D2Cl4, 258C): d=53.0 (t), 117.2 (2îd), 123.5
(q, 1J(C,F)=269.5 Hz), 123.9 (q, 2J(C,F)=32.8 Hz), 125.5 (2îd), 127.4
(2îd), 127.8 (d), 128.6 (d), 133.2 (s), 135.3 (s), 140.4 (s), 155.3 ppm (s);
IR (Nujol): n˜ =3331 (NH), 1667 cmꢀ1 (C=O); elemental analysis calcd
(%) for C45H36F9N7O3 (893.8): C 60.47, H 4.06, N 10.97; found: C 60.20,
H 4.13, N 10.94.
Tris{2-[N’-(4-butylphenyl)ureido]benzyl}amine (3c): The title compound
was prepared in 77% yield according to the general procedure to afford
3c as colorless prisms (an analytical sample was obtained by recrystalliza-
tion from 1:1 CHCl3/Et2O). M.p. 227 2318C; 1H NMR (300 MHz,
[D6]DMSO, 258C, TMS, only monomer was observed): d=0.89 (t,
3J(H,H)=7.2 Hz, 9H), 1.29 (m, 3J(H,H)=7.3 Hz, 6H), 1.51 (m,
3J(H,H)=7.5 Hz, 6H), 2.50 (t, 3J(H,H)=7.7 Hz, 6H), 3.64 (s, 6H), 7.01
7.06 (m, 9H), 7.16 (t, 3J(H,H)=7.4 Hz, 3H), 7.31 (d, 3J(H,H)=8.7 Hz,
6H), 7.55 7.58 (m, 6H), 7.90 (s, 3H), 8.66 ppm (s, 3H); 1H NMR
(300 MHz, CDCl3, 258C, TMS, only dimer was observed): d=0.90 0.95
(m, 18H), 1.17 1.22 (m, 24H), 2.13 (t, 3J(H,H)=7.2 Hz, 12H), 3.11 (d,
2J(H,H)=15.0 Hz, 6H), 3.22 (d, 2J(H,H)=15.0 Hz, 6H), 6.17 (d,
3J(H,H)=8.4 Hz, 12H), 6.41 (d, 3J(H,H)=8.4 Hz, 12H), 7.13 (dd,
3J(H,H)=7.7 Hz, 4J(H,H)=1.4 Hz, 6H), 7.20 (td, 3J(H,H)=7.4 Hz,
4J(H,H)=1.3 Hz, 6H), 7.26 (td, 3J(H,H)=7.4 Hz, 4J(H,H)=1.7 Hz, 6H),
7.37 (s, 6H), 7.64 (d, 3J(H,H)=7.5 Hz, 6H), 8.05 ppm (s, 6H); 13C NMR
(75 MHz, [D6]DMSO, 258C): d=13.8 (q), 21.7 (t), 33.2 (t), 34.1 (t), 54.4
(t), 118.3 (2îd), 123.7(d), 123.9 (d), 127.1 (d), 128.4 (2îd), 128.7 (d),
130.0 (s), 135.6 (s), 137.1 (s), 137.3 (s), 153.1 ppm (s); 13C NMR (50 MHz,
CDCl3, 258C): d=14.1 (q), 22.4 (t), 33.6 (t), 34.6 (t), 53.2 (t), 117.7 (2î
d), 126.58 (d), 126.63 (d), 127.9 (d), 128.2 (2îd), 128.9 (d), 134.6 (s),
135.5 (s), 136.4 (s), 136.6 (s), 155.9 ppm (s); IR (Nujol): n˜ =3317 (NH),
1658 cmꢀ1 (C=O); MS (FAB+): m/z (%): 858 (35) [M++1], 281 (100); el-
emental analysis calcd (%) for C54H63N7O3 (858.1): C 75.58, H 7.40, N
11.43; found: C 75.39, H 7.64, N 11.56.
3
3
General procedure for the synthesis of tris(ureas) 3g k: The correspond-
ing tris(amine) 2 (0.30 mmol) was dissolved in dry CHCl3 (5 mL) and the
isocyanate (0.90 mmol) was added under N2. After stirring at reflux for
18 h the solvent was removed (308C/75 Torr) and Et2O (5 mL) was
added. The white solid was filtered and dried under vacuum. Further pu-
rification was conducted by recrystallization from the appropriate mix-
ture of solvents (except for 3j).
Tris{5-methyl-2-[N’-(4-butylphenyl)ureido]benzyl}amine (3d): The title
compound was prepared in 77% yield according to the general proce-
dure to afford 3d as colorless prisms (an analytical sample was obtained
by recrystallization from 1:2 CHCl3/Et2O). M.p. 252 2548C; 1H NMR
(300 MHz, [D6]DMSO, 258C, TMS, only monomer was observed): d=
0.89 (t, 3J(H,H)=7.4 Hz, 9H), 1.28 (m, 3J(H,H)=7.4 Hz, 6H), 1.51 (m,
Tris{2-[N’-(benzyl)ureido]benzyl}amine (3g): The title compound was
prepared in 81% yield according to the general procedure to afford 3g
as colorless prisms (an analytical sample was obtained by recrystallization
1
from 1:3 CHCl3/Et2O). M.p. 205 2078C; H NMR (200 MHz, [D6]DMSO,
1393
Chem. Eur. J. 2004, 10, 1383 1397
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. AlajarÌn et al.
FULL PAPER
258C, TMS, only monomer was observed): d=3.53 (s, 6H), 4.25 (d,
3J(H,H)=5.7 Hz, 6H), 6.77 (t, 3J(H,H)=5.7 Hz, 3H), 6.98 (t, 3J(H,H)=
7.3 Hz, 3H), 7.15 (t, 3J(H,H)=7.7 Hz, 3H), 7.23 7.36 (m, 15H), 7.46 (d,
3J(H,H)=7.3 Hz, 3H), 7.60 (d, 3J(H,H)=7.9 Hz, 3H), 7.87 ppm (s, 3H);
1H NMR (300 MHz, CDCl3, 258C, TMS, 84:16 mixture of dimer and
monomer was observed): d(dimer)=2.60 (dd, 2J(H,H)=15.4 Hz,
3J(H,H)=3.0 Hz, 6H), 3.78 (d, 2J(H,H)=15.8 Hz, 6H), 3.94 (d,
2J(H,H)=15.8 Hz, 6H), 4.12 (dd, 2J(H,H)=15.4 Hz, 3J(H,H)=9.1 Hz,
6H), 6.05 (dd, 3J(H,H)=9.1 Hz, 3J(H,H)=3.0 Hz, 6H), 7.03 (dd,
3J(H,H)=7.4 Hz, 4J(H,H)=1.5 Hz, 12H), 7.15 7.39 (m, 36H), 7.64 (s,
6H), 8.18 ppm (d, 3J(H,H)=7.8 Hz, 6H); d(monomer)=3.50 (s, 6H),
4.26 (d, 3J(H,H)=5.8 Hz, 6H), 5.12 (t, 3J(H,H)=5.8 Hz, 3H), 6.31 ppm
(s, 3H), the rest of the signals are overlapped with those corresponding
to the dimer; 13C NMR (75 MHz, [D6]DMSO, 258C): d=43.0 (t), 54.3 (t),
122.85 (d), 122.91 (d), 126.7 (d), 127.07 (d), 127.13 (2îd), 128.2 (2îd),
128.8 (d+s), 137.9 (s), 140.1 (s), 155.5 ppm (s); 13C NMR (75 MHz,
CDCl3, 258C): d(dimer)=42.8 (t), 53.8 (t), 126.6 (d), 126.79 (d), 126.80
(d), 127.0 (2îd), 127.2 (d), 128.2 (2îd), 129.0 (d), 135.1 (s), 136.2 (s),
139.3 (s), 158.2 ppm (s); d(monomer)=44.2 (t), 56.5 (t), 122.3 (d), 123.2
(d), 125.8 (s), 127.3 (d), 128.0 (2îd), 128.5 (2îd), 129.4 (d), 132.3 (d),
137.8 (s), 138.8 (s), 155.0 ppm (s); IR (Nujol): n˜ =3334 (NH), 3265 (NH),
1643 cmꢀ1 (C=O); IR (CHCl3, 16.4 mm): n˜ =3327 (NH), 1647 cmꢀ1 (C=
O); MS (FAB+): m/z (%): 732 (25) [M++1], 731 (49) [M+], 220 (100),
132 (41); elemental analysis calcd (%) for C45H45N7O3 (731.9): C 73.85, H
6.20, N 13.40; found: C 73.65, H 6.30, N 13.49.
5.79 (ddt, 3J(H,H)=17.1 Hz, 3J(H,H)=10.2 Hz, 3J(H,H)=5.0 Hz, 6H),
6.35 (s, 3H), 7.07 (t, 3J(H,H)=7.5 Hz, 3H), 7.73 ppm (d, 3J(H,H)=
7.5 Hz, 3H), the rest of the signals are overlapped with those correspond-
ing to the dimer; 13C NMR (50 MHz, [D6]DMSO, 258C): d=41.7 (t), 54.3
(t), 114.8 (t), 123.0 (2îd), 127.1 (d), 128.7 (d), 128.9 (s), 136.1 (d), 137.8
(s), 155.3 ppm (s); 13C NMR (75 MHz, CDCl3, 258C): d(dimer)=41.6 (t),
53.5 (t), 115.2 (t), 126.46 (d), 126.50 (d), 126.8 (d), 128.5 (d), 134.7 (s),
134.8 (d), 135.6 (s), 157.7 ppm (s); d(monomer)=42.3(t), 56.2 (t), 115.8
(t), 122.7 (d), 123.4 (d), 126.4 (s), 129.1 (d), 132.2 (d), 134.6 (d), 137.5 (s),
154.9 ppm (s); IR (Nujol): n˜ =3357 (NH), 3248 (NH), 1651 (C=O),
1643 cmꢀ1 (C=O); elemental analysis calcd (%) for C33H39N7O3 (581.7):
C 68.14, H 6.76, N 16.86; found: C 67.74, H 6.69, N 17.11.
Tris{5-methyl-2-[N’-(propyl)ureido]benzyl}amine (3j): The title com-
pound was prepared according to the above general procedure. However,
after removal of the solvent from the reaction mixture, the crude product
was purified by silica gel chromatography eluting with 1:2 AcOEt/hex-
anes (Rf =0.18) to afford 3j in 80% yield. An analytical sample (colorless
prisms) was obtained by recrystallization from 1:3 CHCl3/Et2O. M.p. 234
2368C; 1H NMR (300 MHz, [D6]DMSO, 258C, TMS, only monomer was
observed): d=0.84 (t, 3J(H,H)=7.5 Hz, 9H), 1.40 (m, 3J(H,H)=7.1 Hz,
6H), 2.21 (s, 9H), 2.95 (q, 3J(H,H)=6.2 Hz, 6H), 3.43 (s, 6H), 6.07 (t,
3J(H,H)=5.4 Hz, 3H), 6.97 (d, 3J(H,H)=8.3 Hz, 3H), 7.05 (s, 3H), 7.37
3
(d, J(H,H)=8.3 Hz, 3H), 7.49 ppm (s, 3H); 1H NMR (300 MHz, CDCl3,
258C, TMS, 80:20 mixture of dimer and monomer was observed):
d(dimer)=0.66 (t, 3J(H,H)=7.4 Hz, 18H), 1.01 1.14 (m, 12H), 1.39 1.51
(m, 6H), 2.38 (s, 18H), 2.76 2.88 (m, 6H), 3.47 (d, 2J(H,H)=15.9 Hz,
6H), 3.68 (d, 2J(H,H)=15.9 Hz, 6H), 5.47 (dd, 3J(H,H)=9.0 Hz,
3J(H,H)=2.7 Hz, 6H), 7.06 (d, 3J(H,H)=8.1 Hz, 6H), 7.20 (d, 3J(H,H)=
8.1 Hz, 6H), 7.38 (s, 6H), 7.77 ppm (s, 6H); d(monomer)=0.90 (t,
3J(H,H)=7.5 Hz, 9H), 2.29 (s, 9H), 3.06 (m, 6H), 4.76 (t, 3J(H,H)=
Tris{5-methyl-2-[N’-(benzyl)ureido]benzyl}amine (3h): The title com-
pound was prepared in 91% yield according to the general procedure to
afford 3h as colorless prisms (an analytical sample was obtained by re-
crystallization from 1:3 CHCl3/Et2O). M.p. 219 2228C; 1H NMR
(300 MHz, [D6]DMSO, 258C, TMS, only monomer was observed): d=
2.18 (s, 9H), 3.49 (s, 6H), 4.22 (d, 3J(H,H)=6.0 Hz, 6H), 6.60 (t,
3J(H,H)=6.0 Hz, 3H), 6.93 (d, 3J(H,H)=8.1 Hz, 3H), 7.07 (d, 3J(H,H)=
1.2 Hz, 3H), 7.22 7.31 (m, 15H), 7.39 (d, 3J(H,H)=8.4 Hz, 3H),
7.79 ppm (s, 3H); 1H NMR (300 MHz, CDCl3, 258C, TMS, a 70:30 mix-
ture of dimer and monomer was observed): d(dimer)=2.44 (s, 18H), 2.54
3
6.2 Hz, 3H), 6.22 (s, 3H), 7.82 ppm (d, J(H,H)=8.1 Hz, 3H), the rest of
the signals are overlapped with those corresponding to the dimer;
13C NMR (75 MHz, [D6]DMSO, 258C): d=11.3 (q), 20.4 (q), 22.8 (t),
41.1 (t), 55.1 (t), 123.3 (d), 128.0 (d), 128.7 (s), 130.9 (d), 131.6 (s), 135.6
(s), 155.8 ppm (s); 13C NMR (75 MHz, CDCl3, 258C): d(dimer)=11.2 (q),
21.5 (q), 23.7 (t), 41.0 (t), 53.7 (t), 126.9 (d), 127.4 (d), 128.6 (d), 133.5
(s), 135.1 (s), 135.7 (s), 158.2 ppm (s); d(monomer)=11.3 (q), 20.6 (q),
23.1 (t), 42.0 (t), 56.7 (t), 121.7 (d), 125.3 (s), 129.9 (d), 132.5 (s), 132.9
(d), 135.4 (s), 155.2 ppm (s); IR (Nujol): n˜ =3357 (NH), 3258 (NH),
1645 cmꢀ1 (C=O); elemental analysis calcd (%) for C36H51N7O3 (629.9):
C 68.65, H 8.16, N 15.57; found: C 68.58, H 8.42, N 15.58.
2
3
2
(dd, J(H,H)=15.5 Hz, J(H,H)=3.4 Hz, 6H), 3.66 (d, J(H,H)=15.6 Hz,
6H), 3.89 (d, 2J(H,H)=15.6 Hz, 6H), 4.15 (dd, 2J(H,H)=15.5 Hz,
3J(H,H)=9.4 Hz, 6H), 6.02 (dd, 3J(H,H)=9.4 Hz, J(H,H)=3.4 Hz, 6H),
3
6.92 7.03 (m, 18H), 7.11 7.34 (m, 24H), 7.61 (s, 6H), 7.92 ppm (s, 6H);
d(monomer)=2.19 (s, 9H), 3.44 (s, 6H), 4.24 (d, 3J(H,H)=5.8 Hz, 6H),
5.01 (t, 3J(H,H)=5.8 Hz, 3H), 6.22 (s, 3H), 6.76 (dd, 3J(H,H)=8.3 Hz,
4J(H,H)=1.8 Hz, 3H), 7.52 ppm (d, 3J(H,H)=8.3 Hz, 3H), the rest of
the signals are overlapped with those corresponding to the dimer;
13C NMR (75 MHz, [D6]DMSO, 258C): d=20.4 (q), 43.0 (t), 54.7 (t),
123.2 (d), 126.6 (d), 127.1 (2îd), 127.9 (d), 128.1 (2îd), 128.9 (s), 130.5
(d), 131.8 (s), 135.4 (s), 140.1 (s), 155.8 ppm (s); 13C NMR (75 MHz,
CDCl3, 258C): d(dimer)=21.7 (q), 42.7 (t), 53.9 (t), 126.7 (3îd), 127.0
(d), 127.8 (d), 128.2 (2îd), 128.8 (d), 133.5 (s), 135.0 (s), 135.9 (s), 139.5
(s), 158.3 ppm (s); d(monomer)=20.6 (q), 44.1 (t), 56.5 (t), 122.2 (d),
125.8 (d), 127.2 (d), 128.0 (2îd), 128.5 (2îd), 129.9 (d), 132.7 (s), 132.8
(s), 135.2 (s), 139.0 (s), 155.0 ppm (s); IR (Nujol): n˜ =3338 (NH), 3252
(NH), 1650 (C=O), 1645 cmꢀ1 (C=O); MS (FAB+): m/z (%): 774 (17)
[M++1], 773 (29) [M+], 233 (51), 123 (100); elemental analysis calcd
(%) for C48H51N7O3 (774.0): C 74.49, H 6.64, N 12.67; found: C 74.20, H
7.03, N 12.67.
Tris{5-methyl-2-[N’-(1-phenylethyl)ureido]benzyl}amine (3k): The title
compound was prepared in 62% yield according to the general proce-
dure to afford 3k as colorless prisms (an analytical sample was obtained
by recrystallization from 1:1 CH2Cl2/Et2O). M.p. 235 2388C; [a]D25
=
ꢀ32.96 (c=0.2 in CHCl3) for the reaction with (S)-a-methylbenzyl isocy-
anate; 1H NMR (300 MHz, [D6]DMSO, 258C, TMS, only monomer was
observed): d=1.27 (d, 3J(H,H)=6.8 Hz, 9H), 2.22 (s, 9H), 3.14 (d,
2J(H,H)=12.8 Hz, 3H), 3.73 (d, 2J(H,H)=12.8 Hz, 3H), 4.72 (m,
3J(H,H)=6.8 Hz, 3H), 6.53 (d, 3J(H,H)=6.8 Hz, 3H), 6.92 (d, 3J(H,H)=
8.1 Hz, 3H), 7.10 (s, 3H), 7.17 7.22 (m, 9H), 7.25 7.30 (m, 9H),
7.47 ppm (s, 3H); 1H NMR (300 MHz, CDCl3, 258C, TMS, only mono-
mer was observed): d=1.35 (d, 3J(H,H)=4.5 Hz, 9H), 2.22 (s, 9H), 3.37
(brs, 6H), 4.73 (brs, 3H), 5.34 (brs, 3H), 6.47 (brs, 3H), 6.84 (d,
3J(H,H)=7.8 Hz, 3H), 6.95 (s, 3H), 7.20 7.29 (m, 15H), 7.39 ppm (brs,
3H); 13C NMR (75 MHz, [D6]DMSO, 258C): d=20.4 (q), 22.9 (q), 49.0
(d), 55.6 (t), 123.7 (d), 125.6 (2îd), 126.4 (d), 128.1 (2îd), 128.2 (d),
128.6 (s), 131.3 (d), 131.7 (s), 135.4 (s), 145.3 (s), 155.1 ppm (s); IR
(Nujol): n˜ =3406 (NH), 3333 (NH), 3221 (NH), 1699 (C=O), 1647 cmꢀ1
(C=O); elemental analysis calcd (%) for C51H57N7O3 (816.1): C 75.06, H
7.04, N 12.02; found: C 74.83, H 6.99, N 12.11.
Tris{2-[N’-(2-propenyl)ureido]benzyl}amine (3i): The title compound was
prepared in 58% yield according to the general procedure to afford 3i as
1
colorless prisms. M.p. 249 2528C; H NMR (200 MHz, [D6]DMSO, 258C,
TMS, only monomer was observed): d=3.53 (s, 6H), 3.69 (t, 3J(H,H)=
3
2
5.3 Hz, 6H), 5.07 (dd, J(H,H)=10.3 Hz, J(H,H)=1.6 Hz, 3H), 5.16 (dd,
3J(H,H)=17.4 Hz, 2J(H,H)=1.6 Hz, 3H), 5.84 (ddt, 3J(H,H)=17.4 Hz,
3J(H,H)=10.3 Hz, 3J(H,H)=5.3 Hz, 3H), 6.40 (t, 3J(H,H)=5.3 Hz, 3H),
7.02 (t, 3J(H,H)=7.1 Hz, 3H), 7.18 (t, 3J(H,H)=7.3 Hz, 3H), 7.47 (d,
3J(H,H)=6.8 Hz, 3H), 7.58 (d, 3J(H,H)=7.7 Hz, 3H), 7.78 ppm (s, 3H);
1H NMR (300 MHz, C2D2Cl4, 258C, TMS, a 77:23 mixture of dimer and
monomer was observed): d(dimer)=2.17 2.23 (m, 6H), 3.32 3.36 (m,
6H), 3.56 (d, 2J(H,H)=15.8 Hz, 6H), 3.73 (d, 2J(H,H)=15.8 Hz, 6H),
4.80 (d, 3J(H,H)=10.2 Hz, 6H), 4.90 (d, 3J(H,H)=17.1 Hz, 6H), 5.30
5.43 (m, 6H), 5.53 (dd, 3J(H,H)=8.1 Hz, 3J(H,H)=3.6 Hz, 6H), 7.29
Tris{5-methyl-2-[N’-(1-methylethyl)ureido]benzyl}amine (3l): A mixture
of tris(amine) 2b (0.10 g, 0.27 mmol) and isopropyl isocyanate (0.14 g,
1.60 mmol) was dissolved in dry DMF (10 mL) under N2 and stirred at
808C for 18 h. After cooling, the reaction mixture was poured in H2O
(20 mL) and extracted with CH2Cl2 (3î10 mL). The combined organic
extracts were washed with H2O (3î20 mL) and dried over MgSO4. The
solvent was then removed (308C/75 Torr) and the crude product was pu-
rified by silica gel chromatography eluting with 1:1 AcOEt/hexanes (Rf =
0.41) to afford 3l in 64% yield. An analytical sample (colorless prisms)
was obtained by recrystallization from 1:3 CHCl3/Et2O. M.p. 228 2298C;
3
7.35 (m, 18H), 7.43 (s, 6H), 8.04 ppm (d, J(H,H)=7.2 Hz, 6H); d(mono-
mer)=3.53 (s, 6H), 3.88 (t, 3J(H,H)=5.0 Hz, 6H), 5.12 5.19 (m, 9H),
1394
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1383 1397

Tris(2-ureidobenzyl)amine Self-Assembly
1383 1397
1H NMR (300 MHz, [D6]DMSO, 258C, TMS, only monomer was ob-
served): d=1.04 (d, 3J(H,H)=6.3 Hz, 18H), 2.22 (s, 9H), 3.40 (s, 6H),
3.68 (m, 3J(H,H)=6.7 Hz, 3H), 5.97 (d, 3J(H,H)=7.5 Hz, 3H), 7.00 (d,
3J(H,H)=8.1 Hz, 3H), 7.06 (s, 3H), 7.29 (s, 3H), 7.38 ppm (d, 3J(H,H)=
C27H33N7O3 (503.6): C 64.40, H 6.60, N 19.47; found: C 64.08, H 6.43, N
19.81.
2-Nitrobenzyl iodide: NaI (0.44 g, 2.90 mmol) was added to a solution of
2-nitrobenzyl chloride (0.25 g, 1.45 mmol) in dry acetone (5 mL) and the
reaction mixture was stirred at 208C for 20 h. The solid was then filtered
and washed with cold acetone (5î5 mL). The filtrate was collected, the
solvent removed (308C/75 Torr), and the residue purified by silica gel
chromatography eluting with 1:9 AcOEt/hexanes (Rf =0.49) to afford the
title compound as yellow prisms in 96% yield. M.p. 74 758C (lit.: 73
758C);[29] 1H NMR (300 MHz, CDCl3, 258C, TMS): d=4.79 (s, 2H), 7.41
7.59 (m, 3H), 8.03 ppm (d, 3J(H,H)=7.8 Hz, 1H); IR (Nujol): n˜ =1520
1
8.1 Hz, 3H); H NMR (300 MHz, CDCl3, 258C, TMS, only monomer was
3
observed): d=1.13 (d, J(H,H)=6.6 Hz, 18H), 2.28 (s, 9H), 3.43 (s, 6H),
3.86 (m, 3J(H,H)=6.7 Hz, 3H), 4.76 (d, 3J(H,H)=7.2 Hz, 3H), 6.36 (s,
3
3
3H), 6.99 (s, 3H), 7.08 (d, J(H,H)=8.1 Hz, 3H), 7.84 ppm (d, J(H,H)=
8.1 Hz, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=20.6 (q), 22.8 (2îq),
42.2 (d), 56.9 (t), 122.1 (d), 125.2 (s), 129.8 (d), 132.3 (s), 132.8 (d), 135.2
(s), 154.4 ppm (s); IR (Nujol): n˜ =3384 (NH), 3375 (NH), 3265 (NH),
1699 (C=O), 1660 cmꢀ1 (C=O); elemental analysis calcd (%) for
C36H51N7O3 (629.9): C 68.65, H 8.16, N 15.57; found: C 68.39, H 8.30, N
15.71.
(NO2), 1340 (NO2), 1171, 793, 759, 696 cmꢀ1
.
Bis(2-nitrobenzyl)(2-azidobenzyl)amine (7): 2-Azidobenzylamine (1.60 g,
10.8 mmol) and 2-nitrobenzyl iodide (5.68 g, 21.6 mmol) in dry acetoni-
trile (2 and 5 mL, respectively) were added to a suspension of Na2CO3
(6.58 g, 62.1 mmol) in the same solvent (10 mL) and the reaction mixture
was stirred at reflux for 24 h. After cooling, the inorganic salts were fil-
tered and washed with cold acetonitrile (5î5 mL). The filtrate was col-
lected, the solvent removed (308C/75 Torr), and the residue was purified
by silica gel chromatography eluting with 1:9 AcOEt/hexanes (Rf =0.21)
to afford 7 as a yellow oil in 91% yield. 1H NMR (200 MHz, CDCl3,
258C, TMS): d=3.55 (s, 2H), 3.91 (s, 4H), 7.04 7.11 (m, 2H), 7.22 7.37
(m, 4H), 7.51 (td, 3J(H,H)=7.5 Hz, 4J(H,H)=1.3 Hz, 2H), 7.65 (dd,
3J(H,H)=7.7 Hz, 4J(H,H)=1.1 Hz, 2H), 7.78 ppm (dd, 3J(H,H)=8.0 Hz,
4J(H,H)=1.3 Hz, 2H); 13C NMR (50 MHz, CDCl3, 258C): d=54.2 (t),
55.6 (2ît), 118.1 (d), 124.3 (2îd), 124.6 (d), 127.9 (2îd), 128.6 (s), 128.9
(d), 131.0 (2îd), 131.4 (d), 132.6 (2îd), 134.1 (2îs), 138.9 (s), 149.6 ppm
(2îs); IR (neat): n˜ =2131 (N3), 1531 (NO2), 1522, 1342 cmꢀ1 (NO2); MS
(70 eV, EI): m/z (%): 420 (40) [M++2], 419 (43) [M++1], 418 (11) [M+],
286 (66), 105 (100); elemental analysis calcd (%) for C21H18N6O4 (418.4):
C 60.28, H 4.34, N 20.09; found: C 60.01, H 4.50, N 20.45.
Tris{2-[N’-(2,6-dimethylphenyl)ureido]benzyl}amine (3m): A mixture of
tris(2-aminobenzyl)amine (2a) (0.13 g, 0.39 mmol) and 2,6-dimethylphen-
yl isocyanate (0.17 g, 1.18 mmol) was dissolved in dry DMF (15 mL)
under N2 and stirred at 808C for 10 h. After cooling, the reaction mixture
was poured in H2O (40 mL) and the white solid was filtered, washed with
H2O and subsequently with Et2O to afford 3m as colorless prisms in
77% yield. M.p. 246 2488C; 1H NMR (300 MHz, [D6]DMSO, 258C,
TMS, only monomer was observed): d=2.22 (s, 18H), 3.67 (s, 6H), 7.06
(m, 12H), 7.20 (t, 3J(H,H)=7.5 Hz, 3H), 7.54 (m, 3H), 7.64 (d,
3J(H,H)=8.1 Hz, 3H), 7.89 (s, 3H), 8.16 ppm (s, 3H); 1H NMR
(300 MHz, CDCl3, 258C, TMS, only monomer was observed): d=2.09 (s,
18H), 3.64 (s, 6H), 6.24 (brs, 3H), 7.01 7.15 (m, 15H), 7.22 7.25 (m,
6H), 7.62 ppm (brs, 3H); 13C NMR (75 MHz, [D6]DMSO, 258C): d=18.2
(2îq), 54.2 (t), 123.2 (d), 123.4 (d), 126.0 (d), 127.0 (d), 127.7 (2îd),
128.4 (d), 129.5 (s), 135.3 (s), 135.6 (2îs), 137.7 (s), 153.6 ppm (s); IR
(Nujol): n˜ =3273 (NH), 1634 cmꢀ1 (C=O); MS (FAB+): m/z (%): 774
(30) [M++1], 253 (100), 132 (29); elemental analysis calcd (%) for
C48H51N7O3 (774.0): C 74.49, H 6.64, N 12.67; found: C 74.19, H 6.95, N
12.57.
Bis(2-nitrobenzyl)(2-aminobenzyl)amine (8): PMe3 in toluene (1.0m,
11.7 mL, 11.7 mmol) was slowly added at 08C to a solution of 7 (4.10 g,
9.8 mmol) in freshly distilled THF (30 mL) under N2. The reaction mix-
ture was then stirred at this temperature for 20 30 min. H2O (15 mL)
was added and the reaction mixture was stirred at 208C for a further
20 h. After removal of the organic solvent (308C/75 Torr), H2O (40 mL)
was added and the aqueous phase was extracted with CH2Cl2 (3î20 mL).
The combined extracts were dried over MgSO4, the solvent evaporated
(308C/75 Torr), and the residue purified by silica gel chromatography
eluting with 1:4 AcOEt/hexanes (Rf =0.16) to afford 8 (67 90% yield) as
yellow prisms (an analytical sample was obtained by recrystallization
from 1:4 CHCl3/Et2O). M.p. 96 998C; 1H NMR (200 MHz, CDCl3, 258C,
TMS): d=3.55 (s, 2H), 3.85 (s, 4H), 4.13 (s, 2H), 6.53 6.65 (m, 2H),
6.98 7.06 (m, 2H), 7.22 7.31 (m, 2H), 7.37 7.48 (m, 4H), 7.66 ppm (dd,
3J(H,H)=8.1 Hz, 4J(H,H)=1.0 Hz, 2H); 13C NMR (50 MHz, CDCl3,
258C): d=56.3 (2ît), 59.4 (t), 115.6 (d), 117.8 (d), 121.4 (s), 124.2 (2îd),
128.2 (2îd), 128.9 (d), 131.2 (d), 132.0 (2îd), 132.6 (2îd), 133.4 (2îs),
146.5 (s), 149.7 ppm (2îs); IR (Nujol): n˜ =3486 (NH), 3390 (NH), 1623,
1522 (NO2), 1340 cmꢀ1 (NO2); MS (70 eV, EI): m/z (%): 393 (42) [M+
+1], 375 (39), 286 (47), 257 (82), 120 (100); HRMS (EI): m/z: calcd for
C21H20N4O4: 392.148455, found 392.148647.
Tris[2-(methylthiocarbonylamino)benzyl]amine (4): nBuLi (1.6m, 3.5 mL,
5.41 mmol) in hexane was added to a solution of tris(2-aminobenzyl)a-
mine (2a) (0.30 g, 0.90 mmol) and hexamethyldisilazane (0.44 g,
2.71 mmol) in THF (10 mL) at ꢀ788C under N2. The solution was stirred
at ꢀ788C for 0.5 h, followed by addition of a solution of DMDTC
(0.33 g, 2.71 mmol) in THF (5 mL). The solution was then allowed to
react at 208C for 6 h. The reaction was quenched by pouring into ice
water. The crude product was extracted with CH2Cl2 (3î10 mL), washed
with brine (3î10 mL), and dried over MgSO4. After removal of the sol-
vent (308C/75 Torr), Et2O (15 mL) was added and the white solid was fil-
tered and dried under vacuum to afford 4 in 99% yield as colorless
prisms. M.p. 152 1548C; 1H NMR (200 MHz, CDCl3, 258C, TMS): d=
2.33 (s, 9H), 3.49 (s, 6H), 7.08 7.33 (m, 9H), 7.81 7.87 ppm (m, 6H);
13C NMR (50 MHz, CDCl3, 258C): d=12.8 (q), 57.2 (t), 124.1 (d), 125.3
(d), 127.7 (s), 129.0 (d), 131.5 (d), 136.5 (s), 167.4 ppm (s); IR (Nujol):
n˜ =3285 (NH), 1658 cmꢀ1 (C=O); MS (FAB+): m/z (%): 555 (20) [M+
+1], 507 (37), 132 (100).
Tris[2-(N’-methylureido)benzyl]amine (3n): MeNH2 (3.26 mmol, 0.31 g,
33 wt% in EtOH) was added to a solution of the tris(thiocarbamate) 4 in
hot MeOH (25 mL) and the reaction mixture was stirred at reflux for
15 h. After removal of the solvent (308C/75 Torr) Et2O (5 mL) was
added. The white solid was filtered, washed with MeOH (3î2 mL), and
dried under vacuum to afford 3n as colorless prisms in 78% yield. M.p.
266 2688C; 1H NMR (401 MHz, [D6]DMSO, 258C, TMS, only monomer
was observed): d=2.58 (d, 3J(H,H)=4.5 Hz, 9H), 3.48 (s, 6H), 6.13 (q,
3J(H,H)=4.5 Hz, 3H), 7.00 (td, 3J(H,H)=7.5 Hz, 4J(H,H)=1.0 Hz, 3H),
7.16 (td, 3J(H,H)=7.7 Hz, 4J(H,H)=1.1 Hz, 3H), 7.40 (dd, 3J(H,H)=
7.1 Hz, 4J(H,H)=0.9 Hz, 3H), 7.51 (dd, 3J(H,H)=8.0 Hz, 4J(H,H)=
Bis(2-nitrobenzyl){2-[N’-(4-butylphenyl)ureido]benzyl}amine (9a): 4-Bu-
tylphenyl isocyanate (0.22 g, 1.3 mmol) was added to a solution of 8
(0.50 g, 1.3 mmol) in dry CH2Cl2 (35 mL) under N2. After stirring at 208C
for 24 h the solvent was removed (308C/75 Torr) and the residue was pu-
rified by silica gel chromatography eluting with 1:4 AcOEt/hexanes (Rf =
0.21) to afford 9a (98% yield) as yellow prisms (an analytical sample
was obtained by recrystallization from 1:3 CHCl3/Et2O). M.p. 68 708C;
1H NMR (401 MHz, CDCl3, 258C, TMS): d=0.93 (t, 3J(H,H)=7.3 Hz,
3H), 1.36 (m, 3J(H,H)=7.4 Hz, 2H), 1.56 1.63 (m, 2H), 2.59 (t,
3J(H,H)=7.7 Hz, 2H), 3.74 (s, 2H), 3.94 (s, 4H), 6.90 (td, 3J(H,H)=
7.4 Hz, 4J(H,H)=0.9 Hz, 1H), 7.10 7.24 (m, 8H), 7.38 (td, 3J(H,H)=
7.5 Hz, 4J(H,H)=1.1 Hz, 2H), 7.52 (d, 3J(H,H)=8.4 Hz, 2H), 7.60 (dd,
3J(H,H)=8.1 Hz, 4J(H,H)=1.0 Hz, 2H), 7.72 (s, 1H), 7.83 (s, 1H),
8.00 ppm (d, 3J(H,H)=8.1 Hz, 1H); 13C NMR (101 MHz, CDCl3, 258C):
d=14.0 (q), 22.4 (t), 33.9 (t), 35.1 (t), 57.6 (2ît), 61.4 (t), 119.3 (2îd),
121.6 (d), 122.6 (d), 124.5 (2îd), 125.1 (s), 128.4 (2îd), 128.9 (2îd),
129.1 (d), 131.0 (d), 132.1 (2îd), 133.4 (2îd), 133.5 (2îs), 137.0 (s),
137.4 (s), 138.7 (s), 148.8 (2îs), 152.7 ppm (s); IR (Nujol): n˜ =3384
(NH), 1702 (C=O), 1593, 1528 (NO2), 1345 cmꢀ1 (NO2); MS (FAB+): m/z
1
0.7 Hz, 3H), 7.72 ppm (s, 3H); H NMR (401 MHz, C2D2Cl4, 258C, TMS,
only dimer was observed): d=1.85 (d, 3J(H,H)=4.5 Hz, 18H), 3.50 (d,
2J(H,H)=15.8 Hz, 6H), 3.68 (d, 2J(H,H)=15.8 Hz, 6H), 5.33 (q,
3J(H,H)=4.5 Hz, 6H), 7.25 7.29 (m, 18H), 7.43 (s, 6H), 7.98 8.00 ppm
(m, 6H); 13C NMR (101 MHz, [D6]DMSO, 258C): d=26.3 (q), 54.3 (t),
123.0 (d), 123.3 (d), 127.1 (d), 129.2 (d), 129.3 (s), 138.0 (s), 156.2 ppm
(s); 13C NMR (101 MHz, C2D2Cl4, 258C): d=26.2 (q), 53.4 (t), 126.4 (d),
126.5 (d), 126.7 (d), 128.6 (d), 134.7 (s), 135.5 (s), 158.3 ppm (s); IR
(Nujol): n˜ =3379 (NH), 3252 (NH), 1646 cmꢀ1 (C=O); MS (FAB+): m/z
(%): 504 (20) [M++1], 163 (83); elemental analysis calcd (%) for
1395
Chem. Eur. J. 2004, 10, 1383 1397
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

M. AlajarÌn et al.
FULL PAPER
(%): 568 (65) [M+ +1], 567 (11) [M+], 281 (92), 279 (42), 106 (100); ele-
mental analysis calcd (%) for C32H33N5O5 (567.7): C 67.71, H 5.86, N
12.34; found: C 67.36, H 5.90, N 12.41.
Bis(2-{N’-[4-(trifluoromethyl)phenyl]ureido}benzyl){2-[N’-(4-butylphenyl)-
ureido]benzyl}amine (6a): 4-Trifluoromethylphenyl isocyanate (0.09 g,
0.48 mmol) was added to a solution of 10a (0.12 g, 0.24 mmol) in dry
CH2Cl2 (8 mL) under N2. After stirring at 208C for 16 h the solvent was
removed (308C/75 Torr) and Et2O (5 mL) was added. The white solid
was filtered and dried under vacuum to afford 6a (43% yield) as color-
less prisms (an analytical sample was obtained by recrystallization from
1:3 CHCl3/n-pentane). M.p. 243 2478C; 1H NMR (200 MHz, [D6]DMSO,
Bis(2-nitrobenzyl){2-[N’-(4-methoxyphenyl)ureido]benzyl}amine (9b): 4-
Methoxyphenyl isocyanate (0.19 g, 1.3 mmol) was added to a solution of
8 (0.50 g, 1.3 mmol) in dry CH2Cl2 (35 mL) under N2. After stirring at
208C for 24 h the solvent was removed (308C/75 Torr) and the residue
was purified by silica gel chromatography eluting first with 3:7 and subse-
quently with 1:1 AcOEt/hexanes (Rf =0.24 in 3:7 AcOEt/hexanes) to
afford 9b (98% yield) as colorless prisms (an analytical sample was ob-
tained by recrystallization from 1:3 CH2Cl2/Et2O). M.p. 170 1728C;
1H NMR (300 MHz, [D6]DMSO, 258C): d=3.62 (s, 2H), 3.70 (s, 3H),
3.86 (s, 4H), 6.87 (d, 3J(H,H)=9.3 Hz, 2H), 7.03 (t, 3J(H,H)=7.2 Hz,
1H), 7.18 (t, 3J(H,H)=7.2 Hz, 1H), 7.35 7.44 (m, 5H), 7.55 7.62 (m,
3H), 7.75 (d, 3J(H,H)=7.5 Hz, 2H), 7.83 (d, 3J(H,H)=7.8 Hz, 2H), 7.92
(s, 1H), 8.62 ppm (s, 1H); 13C NMR (75 MHz, [D6]DMSO, 258C): d=
54.5 (2ît), 54.8 (t), 55.1 (q), 114.0 (2îd), 120.1 (2îd), 123.1 (d), 123.4
(d), 124.1 (2îd), 127.3 (d), 128.3 (2îd), 129.0 (d), 129.2 (s), 130.6 (2îd),
132.8 (s), 132.9 (2îd+2îs), 137.5 (s), 149.1 (2îs), 153.0 (s), 154.5 ppm
(s); IR (Nujol): n˜ =3386 (NH), 3329 (NH), 1706 (C=O), 1651, 1531
(NO2), 1349 cmꢀ1 (NO2); MS (FAB+): m/z (%): 542 (100) [M++1], 407
(41), 255 (92), 132 (82); elemental analysis calcd (%) for C29H27N5O6
(541.6): C 64.32, H 5.03, N 12.93; found: C 64.29, H 4.91, N 12.99.
3
258C): d=0.83 (t, J(H,H)=7.1 Hz, 3H), 1.23 (m, 3J(H,H)=7.2 Hz, 2H),
1.46 (m, 3J(H,H)=7.1 Hz, 2H), 2.45 (m, 2H), 3.60 (s, 6H), 6.98 7.16 (m,
8H), 7.28 (d, 3J(H,H)=8.0 Hz, 2H), 7.52 7.56 (m, 14H), 7.92 (s, 1H),
8.04 (s, 2H), 8.64 (s, 1H), 9.15 ppm (s, 2H); 13C NMR (50 MHz,
[D6]DMSO, 258C): d=13.8, 21.7, 33.3, 34.2, 54.3, 117.8, 118.4, 121.7 (2î
q, 2J(C,F)=31.9 Hz), 123.9, 124.2, 124.3, 124.6 (2îq, 1J(C,F)=270.8 Hz),
126.1 (4îdq, 3J(C,F)=3.7 Hz), 127.2, 128.5, 128.7, 130.3, 130.6, 135.7,
136.6, 137.0, 137.3, 143.5, 152.8, 153.3 ppm (four signals are overlapped);
19F NMR (188 MHz, [D6]DMSO, 258C): d=ꢀ59.6 ppm; IR (Nujol): n˜ =
3331 (NH), 1667 cmꢀ1 (C=O); MS (FAB+): m/z (%): 882 (53) [M+ +1],
293 (48), 281 (34), 132 (100); elemental analysis calcd (%) for
C48H45F6N7O3 (881.9): C 65.37, H 5.14, N 11.12; found: C 64.97, H 5.51,
N 10.97.
Bis{2-[N’-(4-fluorophenyl)ureido]benzyl}{2-[N’-(4-butylphenyl)ureido]-
benzyl}amine (6b): 4-Fluorophenyl isocyanate (0.07 g, 0.48 mmol) was
added to a solution of 10a (0.12 g, 0.24 mmol) in dry CH2Cl2 (8 mL)
under N2. After stirring at 208C for 16 h the solvent was removed (308C/
75 Torr) and Et2O (5 mL) was added. The white solid was filtered and
dried under vacuum to afford 6b (90% yield) as colorless prisms (an ana-
lytical sample was obtained by recrystallization from 1:1 CHCl3/Et2O).
M.p. 229 2318C; 1H NMR (200 MHz, [D6]DMSO, 258C): d=0.84 (t,
3J(H,H)=7.1 Hz, 3H), 1.24 (m, 3J(H,H)=7.2 Hz, 2H), 1.47 (m,
3J(H,H)=7.3 Hz, 2H), 2.45 (t, 3J(H,H)=7.2 Hz, 2H), 3.61 (s, 6H), 7.00
7.16 (m, 12H), 7.30 (d, 3J(H,H)=8.2 Hz, 2H), 7.37 7.44 (m, 4H), 7.51
7.55 (m, 6H), 7.92 (s, 3H), 8.66 (s, 1H), 8.80 ppm (s, 2H); 13C NMR
(50 MHz, [D6]DMSO, 258C): d=13.8, 21.7, 33.3, 34.2, 54.4, 115.3 (4îdd,
2J(C,F)=22.2 Hz), 118.3, 119.9 (4îdd, 3J(C,F)=7.7 Hz), 123.8, 123.9,
124.0, 127.1, 128.5, 128.6, 130.1, 130.2, 135.7, 136.1 (2îd, 4J(C,F)=
2.3 Hz), 136.9, 137.1, 137.4, 153.15, 153.17, 157.3 ppm (2îd, 1J(C,F)=
238.1 Hz) (four signals are overlapped); 19F NMR (188 MHz, [D6]DMSO,
258C): d=ꢀ121.8 ppm; IR (Nujol): n˜ =3320 (NH), 1654 cmꢀ1 (C=O);
MS (FAB+): m/z (%): 782 (16) [M++1], 243 (17); elemental analysis
calcd (%) for C46H45F2N7O3 (781.9): C 70.66, H 5.80, N 12.54; found: C
70.27, H 6.20, N 12.58.
Bis(2-aminobenzyl){2-[N’-(4-butylphenyl)ureido]benzyl}amine
(10a):
PtO2 (0.28 g, 1.2 mmol) was added to a solution of 9a (0.59 g, 1.0 mmol)
in freshly distilled THF (35 mL) and the reaction mixture was stirred at
208C for 22 h under H2. After filtration over a pad of Celite, the solvent
was removed (308C/75 Torr) and Et2O (5 mL) was added. The white
solid was filtered, dried under vacuum, and purified by silica gel chroma-
tography eluting with 1:3 AcOEt/hexanes (Rf =0.46) to afford 10a (74%
yield) as colorless prisms (an analytical sample was obtained by recrystal-
lization from 1:3 CHCl3/Et2O). M.p. 94 968C; 1H NMR (401 MHz,
CDCl3, 258C, TMS): d=0.93 (t, 3J(H,H)=7.3 Hz, 3H), 1.36 (m,
3J(H,H)=7.4 Hz, 2H), 1.55 1.63 (m, 2H), 2.58 (t, 3J(H,H)=7.7 Hz, 2H),
3.45 (s, 4H), 3.55 (s, 2H), 3.88 (s, 4H), 6.66 (d, 3J(H,H)=7.8 Hz, 2H),
6.76 (t, 3J(H,H)=7.3 Hz, 2H), 6.94 (t, 3J(H,H)=7.1 Hz, 1H), 7.08 7.17
(m, 7H), 7.25 7.28 (m, 1H), 7.39 (d, 3J(H,H)=8.3 Hz, 2H), 8.19 (d,
3J(H,H)=8.1 Hz, 1H), 8.31 (s, 1H), 8.62 ppm (s, 1H); 13C NMR
(101 MHz, CDCl3, 258C): d=14.1 (q), 22.4 (t), 33.9 (t), 35.1 (t), 57.0 (2î
t), 58.4 (t), 116.8 (2îd), 119.39 (2îd), 119.43 (2îd), 120.7 (d), 122.1 (2î
s), 122.2 (d), 124.9 (s), 128.9 (2îd), 129.0 (d), 129.5 (2îd), 131.1 (d),
132.5 (2îd), 137.1 (s), 137.3 (s), 138.4 (s), 144.4 (2îs), 152.9 ppm (s); IR
(Nujol): n˜ =3375 (NH), 3318 (NH), 3252 (NH), 1692 cmꢀ1 (C=O); MS
(FAB +): m/z (%): 508 (14) [M++1], 403 (10), 279 (16), 106 (100); ele-
mental analysis calcd (%) for C32H37N5O (507.7): C 75.71, H 7.35, N
13.79; found: C 75.34, H 7.57, N 13.83.
Bis(2-{N’-[4-(trifluoromethyl)phenyl]ureido}benzyl){2-[N’-(4-methoxy-
phenyl)ureido]benzyl}amine (6c): 4-Trifluoromethylphenyl isocyanate
(0.09 g. 0.50 mmol) was added to a solution of 10b (0.12 g; 0.25 mmol) in
dry CH2Cl2 (15 mL) under N2. After stirring at 208C for 16 h the solvent
was removed (308C/75 Torr) and Et2O (5 mL) was added. The white
solid was filtered and dried under vacuum to afford 6c (44% yield) as
colorless prisms (an analytical sample was obtained by recrystallization
Bis(2-aminobenzyl){2-[N’-(4-methoxyphenyl)ureido]benzyl}amine (10b):
PtO2 (0.29 g, 1.3 mmol) was added to a solution of 9b (0.58 g, 1.1 mmol)
in freshly distilled THF (35 mL) and the reaction mixture was stirred at
208C for 18 h under H2. After filtration over a pad of Celite, the solvent
was removed (308C/75 Torr) and Et2O (5 mL) was added. The white
solid was filtered, dried under vacuum, and purified by silica gel chroma-
tography eluting first with 1:3 and subsequently with 1:1 AcOEt/hexanes
(Rf =0.21 in 1:3 AcOEt/hexanes) to afford 10b (84% yield) as colorless
prisms (an analytical sample was obtained by recrystallization from 1:1
1
from 1:3 CHCl3/Et2O). M.p. 227 2328C; H NMR (300 MHz, [D6]DMSO,
3
258C): d=3.66 (s, 6H), 3.69 (s, 3H), 6.85 (d, J(H,H)=8.7 Hz, 2H), 7.00
3
7.20 (m, 6H), 7.35 (d, J(H,H)=8.7 Hz, 2H), 7.54 7.65 (m, 14H), 7.94 (s,
1H), 8.10 (s, 2H), 8.63 (s, 1H), 9.21 ppm (s, 2H); 13C NMR (75 MHz,
[D6]DMSO, 258C): d=54.5, 54.6, 55.2, 114.0, 117.9, 120.3, 121.8 (2îq,
2J(C,F)=32.0 Hz), 123.9, 124.3, 124.5, 124.6 (2îq, 1J(C,F)=271.0 Hz),
126.0 (4îdq, 3J(C,F)=3.0 Hz), 127.3, 129.25, 129.34, 130.5, 130.8, 132.7,
136.7, 137.2, 143.5, 153.0, 153.7, 154.6 ppm (two signals are overlapped);
19F NMR (188 MHz, [D6]DMSO, 258C): d=ꢀ59.8 ppm; IR (Nujol): n˜ =
3327 (NH), 1666 cmꢀ1 (C=O); MS (FAB+): m/z (%): 856 (46) [M++1],
293 (52), 255 (46), 131 (100); elemental analysis calcd (%) for
C45H39F6N7O4 (855.8): C 63.15, H 4.59, N 11.46; found: C 62.77, H 4.89,
N 11.45.
1
CHCl3/Et2O). M.p. 199 2018C; H NMR (401 MHz, CDCl3, 258C, TMS):
d=3.47 (s, 4H), 3.57 (s, 2H), 3.80 (s, 3H), 3.87 (s, 4H), 6.66 (d,
3J(H,H)=7.7 Hz, 2H), 6.76 (td, 3J(H,H)=7.4 Hz, 4J(H,H)=1.0 Hz, 2H),
6.88 (d, 3J(H,H)=9.0 Hz, 2H), 6.95 (td, 3J(H,H)=7.4 Hz, 4J(H,H)=
1.1 Hz, 1H), 7.08 7.12 (m, 4H), 7.17 (dd, 3J(H,H)=7.5 Hz, 4J(H,H)=
1.3 Hz, 1H), 7.25 7.29 (m, 1H), 7.37 (d, 3J(H,H)=9.0 Hz, 2H), 8.17 (dd,
3J(H,H)=8.2 Hz, 4J(H,H)=0.8 Hz, 1H), 8.26 (s, 1H), 8.40 ppm (s, 1H);
13C NMR (101 MHz, CDCl3, 258C): d=55.6 (q), 57.0 (2ît), 58.4 (t),
114.3 (2îd), 116.8 (2îd), 119.5 (2îd), 120.8 (d), 121.4 (2îd), 122.16
(2îs), 122.24 (d), 125.0 (s), 129.0 (d), 129.5 (2îd), 131.1 (d), 132.56 (s),
132.57 (2îd), 138.5 (s), 144.5 (2îs), 153.1 (s), 155.5 ppm (s); IR (Nujol):
n˜ =3379 (NH), 3306 (NH), 3272 (NH), 1688 cmꢀ1 (C=O); MS (FAB+):
m/z (%): 482 (31) [M++1], 375 (16), 253 (23), 106 (100); elemental anal-
ysis calcd (%) for C29H31N5O2 (481.6): C 72.33, H 6.49, N 14.54; found: C
72.35, H 6.10, N 14.68.
Bis{2-[N’-(4-fluorophenyl)ureido]benzyl}{2-[N’-(4-methoxyphenyl)urei-
do]benzyl}amine (6d): 4-Fluorophenyl isocyanate (0.07 g, 0.50 mmol) was
added to a solution of 10b (0.12 g, 0.25 mmol) in dry CH2Cl2 (8 mL)
under N2. After stirring at 208C for 18h the solvent was removed (308C/
75 Torr) and Et2O (5 mL) was added. The white solid was filtered and
dried under vacuum to afford 6d (91% yield) as colorless prisms. M.p.
1
246 2548C; H NMR (401 MHz, [D6]DMSO, 258C): d=3.60 (s, 6H), 3.69
(s, 3H), 6.82 (d, 3J(H,H)=9.1Hz, 2H), 6.97 7.16 (m, 10H), 7.30 (d,
3J(H,H)=9.0Hz, 2H), 7.38 7.41 (m, 4H), 7.48 7.51 (m, 6H), 7.85 (s,
1396
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 1383 1397

Tris(2-ureidobenzyl)amine Self-Assembly
1383 1397
1H), 7.90 (s, 2H), 8.55 (s, 1H), 8.76 ppm (s, 2H); 13C NMR (101 MHz,
[D6]DMSO, 258C): d=54.5, 54.6, 55.2, 114.0, 115.2 (4îdd, 2J(C,F)=
22.2Hz), 120.0 (4îdd, 3J(C,F)=7.6Hz), 120.2, 123.8, 124.0, 124.2, 124.3,
127.2, 129.2, 130.2, 130.4, 132.7, 136.1 (2îd, 4J(C,F)=2.1Hz), 137.0,
137.2, 153.3, 153.5, 154.5, 157.3 ppm (2îd, 1J(C,F)=238.1Hz) (two sig-
nals are overlapped); 19F NMR (188 MHz, [D6]DMSO, 258C): d=
ꢀ121.1 ppm; IR (Nujol): n˜ =3321 (NH), 1657 cmꢀ1 (C=O); MS (FAB+):
m/z (%): 756 (10) [M++1], 255 (37), 243 (53), 132 (100); elemental anal-
ysis calcd (%) for C43H39F2N7O4 î0.5H2O (784.8): C 67.53, H 5.27, N
12.82; found: C 66.98, H 5.42, N 12.69.
[9] CCDC-219431 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK; fax: (+44)1223-1336-1033; or e-mail: deposit@ccdc.cam.
ac.uk).
[10] a) M. Kitamura, S. Okada, S. Suga, R. Noyori, J. Am. Chem. Soc.
1989, 111, 4028 4036; b) T. W. Kim, M. S. Lah, J.-I. Hong, Chem.
Commun. 2001, 743 744; c) Z. Zhong, A. Ikeda, S. Shinkai, S. Saka-
moto, K. Yamaguchi, Org. Lett. 2001, 3, 1085 1087; d) C. G. Claes-
sens, T. Torres, J. Am. Chem. Soc. 2002, 124, 14522 14523; e) I. Al-
korta, J. Elguero, J. Am. Chem. Soc. 2002, 124, 1488 1493.
[11] a) K. D. Shimizu, J. Rebek, Jr. Proc. Natl. Acad. Sci. USA 1995, 92,
12403 12407; b) R. K. Castellano, D. M. Rudkevich, J. Rebek, Jr. J.
Am. Chem. Soc. 1996, 118, 10002 10003.
Acknowledgement
[12] a) J. Scheerder, R. H. Vreekamp, J. F. J. Engbersen, W. Verboom,
J. P. M. van Duynhoven, D. N. Reinhoudt, J. Org. Chem. 1996, 61,
3476 3481; b) J. Dormann, A. Ruoff, J. Schatz, M. O. Vysotsky, V.
Bˆhmer, J. Chem. Soc. Perkin Trans. 2 2002, 83 87.
[13] a) M. Scherer, J. L. Sessler, M. Moini, A. Gebauer, V. Lynch, Chem.
Eur. J. 1998, 4, 152 158; b) S. A. Hofstadler, R. H. Griffey, Chem.
Rev. 2001, 101, 377 390.
[14] K. C. Russell, E. Leize, A. Van Dorsselaer, J.-M. Lehn, Angew.
Chem. 1995, 107, 244 248; Angew. Chem. Int. Ed. Engl. 1995, 34,
209 213.
[15] X. Cheng, Q. Gao, R. D. Smith, E. E. Simanek, M. Mammen, G. M.
Whitesides, J. Org. Chem. 1996, 61, 2204 2206.
This work was supported by MCYT-FEDER (Project BQU2001 0010)
and FundaciÛn Sÿneca-CARM (Project PI-1/00749/FS/01). J.W.S. thanks
the EPSRC and King×s College London for funding the diffractometer
system and the Nuffield Foundation for the provision of computing
equipment. A.P. is grateful to the Ministerio de Ciencia y TecnologÌa of
Spain for a RamÛn y Cajal contract, and R.-A.O. thanks the Ministerio
de EducaciÛn, Cultura y Deporte of Spain for a fellowship.
[1] J.-M. Lehn, Supramolecular Chemistry: Concepts and Perspectives,
VCH, Weinheim, 1995, pp. 11 13.
[2] a) M. AlajarÌn, P. Molina, A. LÛpez-Lµzaro, C. Foces-Foces, Angew.
Chem. 1997, 109, 147 150; Angew. Chem. Int. Ed. Engl. 1997, 36,
67 70; b) M. AlajarÌn, A. LÛpez-Lµzaro, A. Vidal, J. Bernµ, Chem.
Eur. J. 1998, 4, 2558 2570; c) M. AlajarÌn, A. Vidal, C. LÛpez-Leo-
nardo, J. Bernµ, M. C. RamÌrez de Arellano, Tetrahedron Lett. 1998,
39, 7807 7810; d) M. AlajarÌn, C. LÛpez-Leonardo, A. Vidal, J.
Bernµ, J. W. Steed, Angew. Chem. 2002, 114, 1253 1256; Angew.
Chem. Int. Ed. 2002, 41, 1205 1208.
[3] a) M. C. Etter, Z. UrbaÊczyk-Lipkowska, M. Zia-Ebrahimi, T. W.
Panunto, J. Am. Chem. Soc. 1990, 112, 8415 8426; b) X. Zhao, Y.-L.
Chang, F. W. Fowler, J. W. Lauher, J. Am. Chem. Soc. 1990, 112,
6627 6634; c) J. S. Nowick, V. Antonovich, G. Noronha, J. W. Ziller,
J. Org. Chem. 1995, 60, 1888 1890; d) J. J. Kane, R.-F. Liao, J. W.
Lauher, F. W. Fowler, J. Am. Chem. Soc. 1995, 117, 12003 12004;
e) Y. Tobe, S. Sasaki, M. Mizuno, K. Hirose, K. Naemura, J. Org.
Chem. 1998, 63, 7481 7489; f) S. Pulacchini, I. Abrahams, J. Eames,
M. Watkinson, Supramol. Chem. 2002, 14, 353 357.
[16] a) K. A. Jolliffe, M. Crego Calama, R. Fokkens, N. M. M. Nibbering,
P. Timmerman, D. N. Reindhoudt, Angew. Chem. 1998, 110, 1294
1297; Angew. Chem. Int. Ed. 1998, 37, 1247 1251; b) P. Timmerman,
K. A. Jolliffe, M. Crego Calama, J.-L. Weidmann, L. J. Prins, F. Car-
dullo, B. H. M. Snellink-Ruèl, R. H. Fokkens, N. M. M. Nibbering, S.
Shinkai, D. N. Reindhoudt, Chem. Eur. J. 2000, 6, 4104 4115.
[17] a) C. A. Schalley, J. M. Rivera, T. MartÌn, J. SantamarÌa, G. Siuzdak,
J. Rebek, Jr. Eur. J. Org. Chem. 1999, 1325 1331; b) C. A. Schalley,
T. MartÌn, U. Obst, J. Rebek, Jr. J. Am. Chem. Soc. 1999, 121, 2133
2138; c) C. A. Schalley, R. K. Castellano, M. S. Brody, D. M. Rudke-
vich, G. Siuzdak, J. Rebek, Jr. J. Am. Chem. Soc. 1999, 121, 4568
4579.
[18] a) R. S. Meissner, J. Rebek, Jr. J. de Mendoza, Science 1995, 270,
1485 1488; b) R. Meissner, X. Garcias, S. Mecozzi, J. Rebek, Jr. J.
Am. Chem. Soc. 1997, 119, 77 85.
[19] M. AlajarÌn, A. Pastor, R.-A. Orenes, J. W. Steed, J. Org. Chem.
2002, 67, 7091 7095.
[4] M. AlajarÌn, A. LÛpez-Lµzaro, A. Pastor, P. D. Prince, J. W. Steed,
R. Arakawa, Chem. Commun. 2001, 169 170.
[20] D. J. Cram, H.-J. Choi, J. A. Bryant, C. B. Knobler, J. Am. Chem.
Soc. 1992, 114, 7748 7765.
[5] a) B. C. Hamann, K. D. Shimizu, J. Rebek, Jr. Angew. Chem. 1996,
108, 1425 1427; Angew. Chem. Int. Ed. Engl. 1996, 35, 1326 1329;
b) R. K. Castellano, B. H. Kim, J. Rebek, Jr. J. Am. Chem. Soc.
1997, 119, 12671 12672; c) R. K. Castellano, C. Nuckolls, J. Re-
bek, Jr. J. Am. Chem. Soc. 1999, 121, 11156 11163; d) J. Rebek, Jr.
Chem. Commun. 2000, 637 643.
[21] The values obtained for the X-ray structure of 3d¥3d were extrapo-
lated to the dimer 3a¥3a.
[22] a) A. Wu, A. Chakraborty, J. C. Fettinger, R. A. Flowers II, L.
Isaacs, Angew. Chem. 2002, 114, 4200 4203; Angew. Chem. Int. Ed.
2002, 41, 4028 4031; b) A. Wu, L. Isaacs, J. Am. Chem. Soc. 2003,
125, 4831 4835.
[6] a) O. Mogck, V. Bˆhmer, W. Vogt, Tetrahedron 1996, 52, 8489
8496; b) M. O. Vysotsky, V. Bˆhmer, Org. Lett. 2000, 2, 3571 3574;
c) M. O. Vysotsky, I. Thondorf, V. Bˆhmer, Angew. Chem. 2000, 112,
1309 1312; Angew. Chem. Int. Ed. 2000, 39, 1264 1267; d) M. O.
Vysotsky, A. Pop, F. Broda, I. Thondorf, V. Bˆhmer, Chem. Eur. J.
2001, 7, 4403 4410.
[7] a) J. J. Gonzµlez, R. Ferdani, E. Albertini, J. M. Blasco, A. Arduini,
A. Pochini, P. Prados, J. de Mendoza, Chem. Eur. J. 2000, 6, 73 80;
b) A. M. RincÛn, P. Prados, J. de Mendoza, J. Am. Chem. Soc. 2001,
123, 3493 3498.
[23] G. Cooke, V. M. Rotello, Chem. Soc. Rev. 2002, 31, 275 286.
[24] A. Pop, M. O. Vysotsky, M. Saadioui, V. Bˆhmer, Chem. Commun.
2003, 1124 1125.
[25] G. M. Sheldrick, SHELXL-97, Program for the Solution of Crystal
Structures, University of Gˆttingen, Gˆttingen (Germany), 1997.
[26] L. J. Barbour, XSeed, Program of the Manipulation and Display of
Crystallographic Models, University of Missouri (Columbia), 1999.
[27] P. v. d. Sluis, A. L. Spek, Acta Crystallogr. 1990, A46, 194.
[28] M.-k. Leung, J.-L. Lai, K.-H. Lau, H.-h. Yu, H.-J. Hsiao, J. Org.
Chem. 1996, 61, 4175 4179.
[8] a) J.-L. Lai, M.-k. Leung, G. H. Lee, J. Org. Chem. 1996, 61, 8364
8365; b) C.-F. Liao, J.-L. Lai, J.-A. Chen, H.-T. Chen, H.-L. Cheng,
G.-R. Her, J.-K. Su, Y. Wang, G. H. Lee, M.-K. Leung, J. Org.
Chem. 2001, 66, 2566 2571.
[29] G. H. Daub, R. N. Castle, J. Org. Chem. 1954, 19, 1571 1574.
Received: September 22, 2003 [F5559]
1397
Chem. Eur. J. 2004, 10, 1383 1397
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim